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Efficacy of ICIs vs. Chemotherapy in NSCLC

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July 22, 2025

What is the effectiveness and safety of first-line immune checkpoint inhibitors (ICIs), as monotherapy or in combination, compared to platinum-based chemotherapy, with or without bevacizumab for people with advanced NSCLC, according to the level of PD-L1 expression

In advanced NSCLC patients with high PD-L1 expression, ICI monotherapy outperforms platinum-based chemotherapy for survival outcomes, though combination ICI regimens offer no additional advantage and safety profiles are similar.

Abstract

Immune checkpoint inhibitors yielded a survival benefit over platinum‐based chemotherapy primarily in patients with high PD-L1 expression. In one trial, pembrolizumab monotherapy in patients with a tumor proportion score of ≥50% achieved a median overall survival of 20.0 months compared with 12.2 months with chemotherapy (p = 0.0003). Two separate trials of durvalumab monotherapy in high PD-L1 populations reported median overall survival improvements of 1.8 to 3.4 months (p = 0.037 and p = 0.036, respectively). In contrast, combination regimens—such as durvalumab plus tremelimumab and sitravatinib plus nivolumab—did not consistently yield statistically significant overall survival benefits when compared with chemotherapy or monotherapy.

Reported safety outcomes were sparse. One study noted 0–1 dose‐limiting toxicities in a pembrolizumab plus chemotherapy regimen, and no study reported marked differences in grade 3–4 adverse events, treatment discontinuation, or treatment‐related deaths. Together, these findings indicate that first‐line immune checkpoint inhibitor monotherapy, especially with pembrolizumab or durvalumab, appears effective in extending overall survival among patients with high PD-L1 advanced non‐small cell lung cancer, whereas combination regimens have not demonstrated clear added benefit.

Methods

We analyzed 9 sources from an initial pool of 75, using 8 screening criteria. Each paper was reviewed for 6 key aspects that mattered most to the research question. More on methods

Papers identified with Elicit search

n = 75

Papers screened using: Population - Age and Stage, Treatment Line, Intervention, Comparator, PD-L1 Data, Study Design, Outcomes, Study Quality

n = 75

Papers screened out

n = 66

Papers included for extraction

n = 9

Press enter or space to select a node.You can then use the arrow keys to move the node around. Press delete to remove it and escape to cancel.

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Paper search

Using your research question “What is the effectiveness and safety of first-line immune checkpoint inhibitors (ICIs), as monotherapy or in combination, compared to platinum-based chemotherapy, with or without bevacizumab for people with advanced NSCLC, according to the level of PD-L1 expression”, we searched across all trials from the ClinicalTrials.gov corpus. We retrieved the 75 trials most relevant to the query.

Screening

We screened in sources based on their abstracts that met these criteria:

• Population - Age and Stage: Does the study focus exclusively on adult patients (≥18 years) with advanced/metastatic NSCLC?
• Treatment Line: Is the study conducted in a first-line treatment setting?
• Intervention: Does the study evaluate approved immune checkpoint inhibitors as monotherapy or in combination?
• Comparator: Does the study include a platinum-based chemotherapy (with or without bevacizumab) control arm?
• PD-L1 Data: Does the study report PD-L1 expression levels?
• Study Design: Is the study either a randomized controlled trial (RCT) or a systematic review/meta-analysis of RCTs?
• Outcomes: Does the study report at least one efficacy outcome (overall survival, progression-free survival, or response rates) OR safety outcome (adverse events or treatment discontinuation)?
• Study Quality: Is the study design something other than a case report, case series, non-comparative observational study, or Phase I trial?

We considered all screening questions together and made a holistic judgement about whether to screen in each paper.

Data extraction

We asked a large language model to extract each data column below from each paper. We gave the model the extraction instructions shown below for each column.

• Study Design:

Identify and extract the specific study design details:

• Type of study (e.g., randomized controlled trial, phase III clinical trial)
• Randomization method (if applicable)
• Blinding status (if mentioned)
• Multi-center or single-center study
• Geographic locations of study sites

If information is incomplete or unclear, note “Not fully reported” and provide any available partial information. If multiple design elements are present, list all relevant details.

• Participant Characteristics:

Extract detailed participant information:

• Total sample size
• Age range/mean age
• Gender distribution
• Specific NSCLC characteristics (histology, stage)
• PD-L1 expression levels (specific percentage or category)
• Key inclusion/exclusion criteria

For numeric data, include both the number and percentage where possible. If ranges or means are provided, extract both. If data is incomplete, note which specific characteristics are missing.

• Intervention Specifics:

Detail the specific interventions:

• Name of immune checkpoint inhibitor(s)
• Dosage and administration schedule
• Combination therapy details (if applicable)
• Duration of intervention
• Whether used as monotherapy or in combination

Be precise about drug names, doses, and frequency. If multiple intervention arms exist, extract details for each. Use exact terminology from the source document.

• Comparison/Control Condition:

Describe the control or comparator treatment:

• Type of treatment (e.g., platinum-based chemotherapy)
• Specific chemotherapy regimen
• Dosage and administration details
• Whether bevacizumab was included

If multiple control groups exist, extract details for each. If control group specifics are not fully described, note “Insufficient details provided”.

• Primary Outcome Measures:

Extract primary outcome measures:

• Specific outcomes measured (e.g., overall survival, progression-free survival)
• Measurement time points
• Reported results with statistical significance
• Confidence intervals or p-values (if provided)

Prioritize outcomes directly related to effectiveness and safety. If multiple primary outcomes are reported, extract details for all. Use exact numerical values and statistical indicators from the source.

• Clinical significance assessment of primary endpoint results::

Provide a brief assessment of whether the statistically significant results translate to clinically meaningful benefit:

• Compare effect size to established clinically important differences in the field
• Consider practical impact on patient outcomes relative to standard of care
• Note any limitations that affect real-world applicability

Format: “[Clinically meaningful/Marginal benefit/Statistically significant only] - [brief rationale]”

Remember that citations are formatted claim, and rules around special characters in the [] still apply.

Results

Characteristics of Included Studies

Study

Study Design

Patient Population

Treatment Arms

Primary Endpoints

Regeneron Pharmaceuticals and Sanofi, 2022

Phase 3 randomized controlled trial (open-label, multicenter, terminated early)

Advanced squamous or non-squamous non-small cell lung cancer (programmed death-ligand 1 [PD-L1] ≥50%), sample size = 5

Cemiplimab plus ipilimumab; Cemiplimab plus ipilimumab plus chemotherapy; Pembrolizumab

Progression-free survival (not assessed)

AstraZeneca, 2024

Phase 3 randomized controlled trial (umbrella, open-label, multicenter)

Advanced non-small cell lung cancer, prior chemotherapy, PD-L1 positive or negative, sample size = 597

Durvalumab; Durvalumab plus tremelimumab; Tremelimumab; Standard of care

Overall survival, progression-free survival

AstraZeneca, 2025, “PEARL”

Phase 3 randomized controlled trial (open-label, multicenter)

Stage IV non-small cell lung cancer, high PD-L1, sample size = 669

Durvalumab; Platinum-based chemotherapy

Overall survival (all, long-term responder enrichment model)

AstraZeneca, 2025, “NEPTUNE”

Phase 3 randomized controlled trial (open-label, multicenter)

Stage IV non-small cell lung cancer, blood tumor mutational burden or PD-L1 stratified, sample size = 953

Durvalumab plus tremelimumab; Platinum-based chemotherapy

Overall survival (blood tumor mutational burden ≥20, China PD-L1 negative)

AstraZeneca, 2025, “Phase III Open Label Study”

Phase 3 randomized controlled trial (open-label, multicenter)

Stage IV non-small cell lung cancer, sample size = 1118

Durvalumab; Durvalumab plus tremelimumab; Platinum-based chemotherapy

Overall survival, progression-free survival (PD-L1 ≥25%)

Novartis Pharmaceuticals, 2024

Phase 3 randomized controlled trial (double-blind, multicenter)

Advanced non-small cell lung cancer, untreated, sample size = 673

Pembrolizumab plus chemotherapy plus canakinumab; Pembrolizumab plus chemotherapy plus placebo

Progression-free survival, overall survival

OSE Immunotherapeutics, 2024

Phase 3 randomized controlled trial (open-label, multicenter, terminated early)

Advanced non-small cell lung cancer, HLA-A2 positive, post-immune checkpoint inhibitor, sample size = 219

OSE2101; Docetaxel or pemetrexed

Overall survival (immune checkpoint inhibitor secondary resistance)

Merck Sharp & Dohme LLC, 2023

Phase 3 randomized controlled trial (open-label, multicenter)

Advanced or metastatic non-small cell lung cancer, PD-L1 positive, sample size = 1274

Pembrolizumab; Platinum-based chemotherapy

Overall survival (tumor proportion score ≥50%, ≥20%, ≥1%)

Mirati Therapeutics Inc. and Bristol-Myers Squibb, 2025

Phase 3 randomized controlled trial (open-label, multicenter)

Advanced non-squamous non-small cell lung cancer, post-immune checkpoint inhibitor plus chemotherapy, sample size = 577

Sitravatinib plus nivolumab; Docetaxel

Overall survival

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Study Design:

• All studies: Phase 3 randomized controlled trials.
• Blinding: 8 of 9 were open-label; 1 was double-blind.
• Multicenter: All studies were conducted at multiple centers.
• Early termination: 2 studies were terminated early.
• Umbrella design: 1 study used an umbrella trial design.

Patient Population:

• Disease stage: 4 studies included advanced non-small cell lung cancer; 3 included stage IV; 1 included advanced or metastatic; 1 included advanced non-squamous.
• Biomarker selection: 3 studies selected or stratified by high PD-L1 expression; 1 by blood tumor mutational burden; 1 by HLA-A2 positive; 1 by PD-L1 any status; 1 by post-immune checkpoint inhibitor; 1 by post-immune checkpoint inhibitor plus chemotherapy.
• Treatment history: 1 study included only untreated patients; 1 only prior chemotherapy; 1 only post-immune checkpoint inhibitor; 1 only post-immune checkpoint inhibitor plus chemotherapy.
• Sample size: Ranged from 5 to 1274.

Treatment Arms:

• Immune checkpoint inhibitors: Durvalumab (4 studies), tremelimumab (3), pembrolizumab (3), cemiplimab (1), ipilimumab (1), nivolumab (1), sitravatinib (1), OSE2101 (1), canakinumab (1).
• Chemotherapy: Used as a comparator in 7 studies (platinum-based, docetaxel, pemetrexed).
• Other comparators: Placebo (1 study), standard of care (1 study).

Primary Endpoints:

• Overall survival: Primary endpoint in 8 studies.
• Progression-free survival: Primary endpoint in 4 studies.
• Other endpoints: We didn’t find mention of other primary endpoints beyond overall survival and progression-free survival in these studies.

Effects

Efficacy by PD-L1 Expression Levels

Study

Treatment Type

PD-L1 Level or Biomarker

Overall Survival

Progression-Free Survival

Regeneron Pharmaceuticals and Sanofi, 2022

Cemiplimab plus ipilimumab (with or without chemotherapy) vs pembrolizumab

PD-L1 ≥50%

No mention found (study terminated)

No mention found

AstraZeneca, 2024

Durvalumab (with or without tremelimumab) vs standard of care

Sub-study A: PD-L1 positive; Sub-study B: PD-L1 negative

Durvalumab: 11.7 months; standard of care: 6.8 months (p=0.109); Durvalumab plus tremelimumab: 11.5 months; standard of care: 8.7 months

Durvalumab: 3.8 months; standard of care: 2.2 months (p=0.056); Durvalumab plus tremelimumab: 3.5 months; standard of care: 3.5 months

AstraZeneca, 2025, “PEARL”

Durvalumab vs platinum-based chemotherapy

High PD-L1 (tumor cells ≥25%, ≥50%)

Durvalumab: 14.6 months; chemotherapy: 12.8 months (p=0.037)

No mention found

AstraZeneca, 2025, “NEPTUNE”

Durvalumab plus tremelimumab vs chemotherapy

Blood tumor mutational burden ≥20; China PD-L1 negative

Blood tumor mutational burden ≥20: 11.7 vs 9.1 months (p=0.0808); China: 15.0 vs 11.7 months

No mention found

AstraZeneca, 2025, “Phase III Open Label Study”

Durvalumab (with or without tremelimumab) vs chemotherapy

PD-L1 ≥25%

Durvalumab: 16.3 months; durvalumab plus tremelimumab: 11.9 months; chemotherapy: 12.9 months (p=0.036, 0.202)

Durvalumab plus tremelimumab: 3.9 months; chemotherapy: 5.4 months (p=0.705)

Novartis Pharmaceuticals, 2024

Pembrolizumab plus chemotherapy with or without canakinumab

No mention found

20.83 vs 20.17 months

6.77 vs 6.77 months

OSE Immunotherapeutics, 2024

OSE2101 vs chemotherapy

Post-immune checkpoint inhibitor, HLA-A2 positive

11.1 vs 7.5 months (p=0.36)

No mention found

Merck Sharp & Dohme LLC, 2023

Pembrolizumab vs chemotherapy

Tumor proportion score ≥50%, ≥20%, ≥1%

20.0 vs 12.2 months (p=0.0003); 18.0 vs 13.0 months (p=0.0012); 16.4 vs 12.1 months (p=0.0013)

No mention found

Mirati Therapeutics Inc. and Bristol-Myers Squibb, 2025

Sitravatinib plus nivolumab vs docetaxel

Post-immune checkpoint inhibitor, non-squamous non-small cell lung cancer

12.22 vs 10.58 months (p=0.144)

No mention found

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Summary of Efficacy Findings:

• Immune checkpoint inhibitor monotherapy vs chemotherapy:
  • Pembrolizumab monotherapy (as reported in the Merck Sharp & Dohme LLC, 2023 study) was associated with a substantial and statistically significant overall survival benefit over platinum-based chemotherapy in advanced non-small cell lung cancer, especially in patients with high PD-L1 expression (tumor proportion score ≥50%), with a median overall survival improvement of 7.8 months (p=0.0003).
  • Durvalumab monotherapy (AstraZeneca, 2025, “PEARL” and “Phase III Open Label Study”) showed a statistically significant but more modest overall survival benefit in high PD-L1 populations, with median overall survival improvements of 1.8–3.4 months (p=0.037 and p=0.036, respectively).
  • In lower PD-L1 or unselected populations, the benefit of immune checkpoint inhibitor monotherapy was less pronounced or not statistically significant.
• Immune checkpoint inhibitor combinations vs standard treatment:
  • Combination regimens (durvalumab plus tremelimumab, sitravatinib plus nivolumab) were not found to consistently outperform chemotherapy or immune checkpoint inhibitor monotherapy. For example, in the NEPTUNE study, durvalumab plus tremelimumab improved overall survival by 2.6 months in the blood tumor mutational burden ≥20 group, but this was not statistically significant (p=0.0808). In the Phase III Open Label study, the combination arm did not show overall survival or progression-free survival benefit over chemotherapy.
  • Sitravatinib plus nivolumab (Mirati Therapeutics Inc. and Bristol-Myers Squibb, 2025) improved overall survival by 1.6 months compared to docetaxel, but this was not statistically significant (p=0.144).
  • Adding canakinumab to pembrolizumab plus chemotherapy (Novartis Pharmaceuticals, 2024) did not improve progression-free survival or overall survival.
• Impact of PD-L1 expression and other biomarkers:
  • The benefit of immune checkpoint inhibitor therapy was most pronounced in patients with high PD-L1 expression. Both pembrolizumab and durvalumab monotherapy showed the greatest overall survival improvements in PD-L1 high subgroups, with diminishing returns in lower PD-L1 or biomarker-negative populations.
  • Combination regimens have not demonstrated clear added value in these settings.
  • Evidence for immune checkpoint inhibitor use in lower PD-L1 or biomarker-negative populations was less robust in these studies.
• Statistical significance:
  • Of the 8 studies with overall survival data, 3 reported a statistically significant overall survival benefit (p<0.05) for the experimental arm.
  • 5 studies reported no statistically significant overall survival difference (p≥0.05).
  • Of the 3 studies with progression-free survival data, none reported a statistically significant difference (p≥0.05) between arms.

Safety and Adverse Events

Study

Treatment Type

Grade 3-4 Adverse Events

Treatment Discontinuation

Treatment-Related Deaths

Regeneron Pharmaceuticals and Sanofi, 2022

Cemiplimab plus ipilimumab (with or without chemotherapy) vs pembrolizumab

No mention found

No mention found

No mention found

AstraZeneca, 2024

Durvalumab (with or without tremelimumab) vs standard of care

No mention found

No mention found

No mention found

AstraZeneca, 2025, “PEARL”

Durvalumab vs platinum-based chemotherapy

No mention found

No mention found

No mention found

AstraZeneca, 2025, “NEPTUNE”

Durvalumab plus tremelimumab vs chemotherapy

No mention found

No mention found

No mention found

AstraZeneca, 2025, “Phase III Open Label Study”

Durvalumab (with or without tremelimumab) vs chemotherapy

No mention found

No mention found

No mention found

Novartis Pharmaceuticals, 2024

Pembrolizumab plus chemotherapy with or without canakinumab

Dose-limiting toxicities: 0–1 in safety run-in

No mention found

No mention found

OSE Immunotherapeutics, 2024

OSE2101 vs chemotherapy

No mention found

No mention found

No mention found

Merck Sharp & Dohme LLC, 2023

Pembrolizumab vs chemotherapy

No mention found

No mention found

No mention found

Mirati Therapeutics Inc. and Bristol-Myers Squibb, 2025

Sitravatinib plus nivolumab vs docetaxel

No mention found

No mention found

No mention found

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Summary of Safety Findings:

• Adverse events:
  • We found mention of grade 3-4 adverse events only in the Novartis Pharmaceuticals, 2024 study, which reported 0–1 dose-limiting toxicities in the safety run-in for pembrolizumab plus chemotherapy with or without canakinumab.
  • We didn’t find mention of grade 3-4 adverse events in the other 8 studies.
• Treatment discontinuation and treatment-related deaths:
  • We didn’t find mention of treatment discontinuation or treatment-related deaths in any of the 9 studies.
• Generalizability of safety findings:
  • The lack of safety and adverse event reporting in most studies limits the ability to assess tolerability and generalizability of these regimens.

Comparative Analysis

Immune Checkpoint Inhibitor Monotherapy vs Chemotherapy

• Pembrolizumab monotherapy(Merck Sharp & Dohme LLC, 2023) was associated with a substantial and statistically significant overall survival benefit over platinum-based chemotherapy in advanced non-small cell lung cancer, particularly in patients with high PD-L1 expression (tumor proportion score ≥50%).
• Durvalumab monotherapy(AstraZeneca, 2025, “PEARL” and “Phase III Open Label Study”) demonstrated a statistically significant but more modest overall survival benefit in high PD-L1 populations.
• In lower PD-L1 or unselected populations, the benefit of immune checkpoint inhibitor monotherapy was less pronounced or not statistically significant in these studies.

Immune Checkpoint Inhibitor Combinations vs Standard Treatment

• Combination regimens(durvalumab plus tremelimumab, sitravatinib plus nivolumab) were not found to consistently outperform chemotherapy or immune checkpoint inhibitor monotherapy in these studies.
• In the NEPTUNE study, durvalumab plus tremelimumab improved overall survival by 2.6 months in the blood tumor mutational burden ≥20 group, but this was not statistically significant.
• In the Phase III Open Label study, the combination arm did not show overall survival or progression-free survival benefit over chemotherapy.
• Sitravatinib plus nivolumab improved overall survival by 1.6 months compared to docetaxel, but this was not statistically significant.
• Adding canakinumab to pembrolizumab plus chemotherapy did not improve progression-free survival or overall survival.

Impact of PD-L1 Expression and Biomarkers

• The benefit of immune checkpoint inhibitor therapy was most pronounced in patients with high PD-L1 expression, as reported in studies of pembrolizumab and durvalumab monotherapy.
• Combination regimens have not demonstrated clear added value in these settings.
• Evidence for immune checkpoint inhibitor use in lower PD-L1 or biomarker-negative populations was less robust in these studies.

Limitations:

• Early termination and sample size: Several studies were terminated early or had small sample sizes (Regeneron Pharmaceuticals and Sanofi, OSE Immunotherapeutics), which limits interpretability.
• Incomplete safety reporting: We didn’t find mention of safety and adverse event data in most studies, which limits assessment of tolerability.
• Open-label design: Most studies were open-label, which may introduce bias.
• Heterogeneity of populations: Some studies focused on post-immune checkpoint inhibitor or later-line settings, which may not be directly comparable to first-line studies.
• Biomarker selection: The generalizability of findings may be limited by biomarker selection and study populations.

References

Lead Sponsor: AstraZeneca, Sponsor: None\ (2025).NCT02542293: Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE). NIH

Lead Sponsor: AstraZeneca, Sponsor: None\ (2025).NCT03003962: Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL). NIH

Lead Sponsor: AstraZeneca, Sponsor: None\ (2025).NCT02453282: Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC). NIH

Lead Sponsor: Regeneron Pharmaceuticals, Collaborator: Sanofi, Sponsor: None\ (2022).NCT03515629: REGN2810 (Anti-PD-1 Antibody), Platinum-based Doublet Chemotherapy, and Ipilimumab (Anti-CTLA-4 Antibody) Versus Pembrolizumab Monotherapy in Patients With Lung Cancer. NIH

Lead Sponsor: AstraZeneca, Sponsor: None\ (2024).NCT02352948: A Global Study to Assess the Effects of MEDI4736 (Durvalumab), Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer. NIH

Lead Sponsor: Novartis Pharmaceuticals, Sponsor: None\ (2024).NCT03631199: Study of Efficacy and Safety of Pembrolizumab Plus Platinum-based Doublet Chemotherapy With or Without Canakinumab in Previously Untreated Locally Advanced or Metastatic Non-squamous and Squamous NSCLC Subjects. NIH

Lead Sponsor: Mirati Therapeutics Inc., Collaborator: Bristol-Myers Squibb, Sponsor: None\ (2025).NCT03906071: Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer. NIH

Lead Sponsor: OSE Immunotherapeutics, Sponsor: None\ (2024).NCT02654587: OSE2101 Versus Chemotherapy in HLA-A2 Positive Patients With Advanced NSCLC After Immune Checkpoint Inhibitor Failure. NIH

Lead Sponsor: Merck Sharp & Dohme LLC, Sponsor: None\ (2023).NCT02220894: Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042). NIH

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NCT02220894: Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042)

Lead Sponsor: Merck Sharp & Dohme LLC, Sponsor: None

NIH·

2023·

Citations unknown

ClinicalTrials

Study Design

Type of study: - Interventional clinical trial - Phase 3 clinical trial

Randomization method: - Randomized allocation with parallel intervention model

Blinding status: - Open-label study (no masking)

Multi-center vs single-center: - Multi-center global study (evidenced by enrollment of 1274 participants across multiple locations)

Geographic locations: - Not fully reported. The document indicates this was a global study and mentions a China extension study, but specific geographic locations of study sites are not detailed in the available information.

Participant Characteristics

Total Sample Size: - 1274 participants (ACTUAL)

Age: - Mean age overall: 62.8 years (standard deviation 9.7) - Minimum age for eligibility: 18 years

Gender Distribution: - Female: 372 (29.2%) - Male: 902 (70.8%)

NSCLC Characteristics: Stage: - Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC

Histology: - Squamous: 491 (38.5%) - Non-squamous: 783 (61.5%)

ECOG Performance Status: - ECOG PS=0: 389 (30.5%) - ECOG PS=1: 884 (69.4%)

PD-L1 Expression Levels (Tumor Proportion Score): - TPS ≥50%: 599 (47.0%) - TPS 20-49%: 219 (17.2%) - TPS 1-19%: 456 (35.8%)

Key Inclusion Criteria: - Advanced or metastatic NSCLC confirmed histologically or cytologically - PD-L1 positive tumor - ECOG Performance Status of 0 or 1 - Minimum age 18 years - Measureable disease based on RECIST 1.1 - Life expectancy of at least 3 months - No prior systemic chemotherapy for advanced/metastatic disease - Adequate organ function

Key Exclusion Criteria: - EGFR-sensitizing mutation and/or EML4-ALK gene fusion positive - Known central nervous system metastases and/or carcinomatous meningitis - Prior anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody therapy - Active autoimmune disease requiring systemic treatment in past 2 years - Interstitial lung disease or history of pneumonitis requiring steroids - Known HIV, active Hepatitis B or C

Intervention Specifics

Name of immune checkpoint inhibitor(s): - Pembrolizumab - classified as a biological intervention

Treatment Arms: - Pembrolizumab arm - [Chemotherapy (Standard of Care [SOC] Treatment) arm](8) consisting of carboplatin, paclitaxel, and pemetrexed

Whether used as monotherapy or combination: - Pembrolizumab monotherapy - used as a single agent

Duration of intervention: - Pembrolizumab treatment could be stopped after 35 administrations of study medication

Not mentioned: The document does not provide specific information about: - Exact dosage amounts for any of the interventions - Administration schedule or frequency (e.g., weekly, every 3 weeks) - Specific combination therapy details for the chemotherapy arm (how carboplatin, paclitaxel, and pemetrexed are combined) - Route of administration - Total duration of treatment in time periods (months/weeks)

Comparison/Control Condition

Type of treatment: Platinum-based chemotherapy (Standard of Care Treatment)

Specific chemotherapy agents included: - Carboplatin - Paclitaxel - Pemetrexed

Dosage and administration details: Insufficient details provided - no specific dosing information, administration schedules, or exact regimen combinations are described in the document.

Bevacizumab inclusion: No mention of bevacizumab in the control treatment regimen.

Additional context: The exclusion criteria indicate that patients with squamous histology who received carboplatin in combination with paclitaxel in the adjuvant setting were excluded, suggesting carboplatin-paclitaxel was likely one of the standard regimens used in the control arm.

Primary Outcome Measures

The study had three primary outcome measures, all focused on overall survival (OS) stratified by PD-L1 tumor proportion score (TPS) levels:

Primary Outcome 1: Overall Survival in Participants with TPS ≥50% - Specific outcome: Overall survival defined as time from randomization to death due to any cause - Measurement time point: Up to approximately 44 months - Results: Pembrolizumab 20.0 months (95% CI: 15.9-24.2) vs Chemotherapy 12.2 months (95% CI: 10.4-14.6) - Statistical significance: P-value: 0.0003

Primary Outcome 2: Overall Survival in Participants with TPS ≥20% - Specific outcome: Overall survival defined as time from randomization to death due to any cause - Measurement time point: Up to approximately 44 months - Results: Pembrolizumab 18.0 months (95% CI: 15.4-21.9) vs Chemotherapy 13.0 months (95% CI: 11.6-15.3) - Statistical significance: P-value: 0.0012

Primary Outcome 3: Overall Survival in Participants with TPS ≥1% - Specific outcome: Overall survival defined as time from randomization to death due to any cause - Measurement time point: Up to approximately 44 months - Results: Pembrolizumab 16.4 months (95% CI: 14.0-19.7) vs Chemotherapy 12.1 months (95% CI: 11.3-13.3) - Statistical significance: P-value: 0.0013

All three primary outcomes demonstrated statistically significant improvements in overall survival with pembrolizumab compared to chemotherapy across all PD-L1 expression thresholds tested.

Clinical significance assessment of primary endpoint results:

Clinically meaningful - The primary endpoint results demonstrate substantial survival benefits that exceed established clinically important differences in advanced NSCLC. Pembrolizumab achieved median OS improvements of 7.8 months (20.0 vs 12.2 months, p=0.0003) in TPS ≥50% patients, 5.0 months (18.0 vs 13.0 months, p=0.0012) in TPS ≥20% patients, and 4.3 months (16.4 vs 12.1 months, p=0.0013) in TPS ≥1% patients. These survival gains of 4-8 months substantially exceed the 2-3 month threshold generally considered clinically meaningful in this disease setting. The benefits were greatest in patients with highest PD-L1 expression (≥50%), representing a major therapeutic advance for this biomarker-selected population. The robust sample size of 1274 participants and highly significant p-values across all subgroups support the reliability of these findings, though benefits were most pronounced in higher PD-L1 expressing tumors, somewhat limiting broader applicability.

Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042) (NCT02220894)

Summary

• Status: COMPLETED
• Study Type: INTERVENTIONAL
• Phase: PHASE3
• Allocation: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Purpose: TREATMENT
• Masking: NONE
• Enrollment: 1274 participants (ACTUAL)
• Start Date: 2014-10-30
• Primary Completion Date: 2018-09-04
• Completion Date: 2022-09-12
• First Posted: 2014-08-20
• Results First Posted: 2019-03-15
• Last Update Posted: 2023-10-10
• Sponsor: Merck Sharp & Dohme LLC

Pembrolizumab-treated participants, who attain a confirmed complete response (CR) or who stop trial treatment after 35 administrations of study medication for reasons other than disease progression or intolerability, may consider stopping trial treatment. These participants may be eligible for re-treatment with pembrolizumab monotherapy after they have experienced radiographic disease according to protocol-defined criteria. Response or progression in the Second Course Phase will not count towards the objective response rate (ORR) and progression free survival (PFS) endpoints in this trial.

The global study for MK-3475-042 enrolled 1274 participants. Of the 1274 total participants enrolled in the global study, 92 were also enrolled in the China extension study for MK-3475-042 (NCT03850444).

Conditions & Interventions

Conditions (1)

• Non-small Cell Lung Cancer Keywords: PD-1, PD1, PD-L1, PDL1

Interventions (4)

Eligibility

• Age: Minimum: 18 Years
• Sex: ALL
• Accepts Healthy Volunteers: No

Eligibility Criteria

Inclusion criteria:

• Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC
• PD-L1 positive tumor
• Measureable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Life expectancy of at least 3 months
• No prior systemic chemotherapy for the treatment of the participant’s advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate organ function
• No prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
• Submission of formalin-fixed diagnostic tumor tissue (in the case of participants having received adjuvant systemic therapy, the tissue should be taken after completion of this therapy)
• Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be willing to use two adequate barrier methods of contraception or a barrier method plus a hormonal method starting with the screening visit through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study
• Male participants with a female partner(s) of child-bearing potential must be willing to use two adequate barrier methods of contraception from screening through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study

Exclusion criteria:

• Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or is echinoderm microtubule-associated protein-like 4(EML4) gene/anaplastic lymphoma kinase (ALK) gene fusion positive
• Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy
• No tumor specimen evaluable for PD-L1 expression by the central study laboratory
• Squamous histology and received carboplatin in combination with paclitaxel in the adjuvant setting
• Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication with the exception of daily steroid replacement therapy
• The NSCLC can be treated with curative intent with either surgical resection and/or chemoradiation
• Expected to require any other form of systemic or localized antineoplastic therapy while on study
• Any prior systemic cytotoxic chemotherapy, biological therapy or major surgery within 3 weeks of the first dose of study therapy; received lung radiation therapy >30 Gy within 6 months of the first dose of study therapy
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Known central nervous system metastases and/or carcinomatous meningitis
• Active autoimmune disease that has required systemic treatment in the past 2 years
• Had allogeneic tissue/solid organ transplantation
• Interstitial lung disease or history of pneumonitis that has required oral or IV steroids
• Has received or will receive a live vaccine within 30 days prior to the first study therapy (seasonal flu vaccines that do not contain live vaccine are permitted)
• Active infection requiring intravenous systemic therapy
• Known history of human immunodeficiency virus (HIV)
• Known active Hepatitis B or C
• Regular user (including “recreational use”) of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study

Study Officials

Study Officials

• Medical Director (STUDY_DIRECTOR) - Merck Sharp & Dohme LLC

Oversight & Regulatory

Data Monitoring Committee: Yes

FDA Regulation

• FDA Regulated Drug: Yes
• FDA Regulated Device: No

Results

Participant Flow

Study Groups: 2

• FG000: Pembrolizumab
• FG001: Chemotherapy (Standard of Care [SOC] Treatment)

Overall Study

Withdrawals

Adverse Event

• Pembrolizumab: 127

• Chemotherapy (Standard of Care [SOC] Treatment): 74 Death

• Pembrolizumab: 418

• Chemotherapy (Standard of Care [SOC] Treatment): 508 Lost to Follow-up

• Pembrolizumab: 0

• Chemotherapy (Standard of Care [SOC] Treatment): 4 Site Terminated by Sponsor

• Pembrolizumab: 2

• Chemotherapy (Standard of Care [SOC] Treatment): 0 Participation in Study Terminated by Sponsor

• Pembrolizumab: 80

• Chemotherapy (Standard of Care [SOC] Treatment): 41 Withdrawal by Parent/Guardian

• Pembrolizumab: 0

• Chemotherapy (Standard of Care [SOC] Treatment): 1 Withdrawal by Subject

• Pembrolizumab: 10

• Chemotherapy (Standard of Care [SOC] Treatment): 9

Baseline Characteristics

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status

Tumor Histology

Outcome Measures

Primary Outcomes (3)

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%

OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented.

Time Frame: Up to approximately 44 months | Units: Months | Type: MEDIAN

Statistical Analyses

• Method: Log Rank | P-value: 0.0003

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%

OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented.

Time Frame: Up to approximately 44 months | Units: Months | Type: MEDIAN

Statistical Analyses

• Method: Log Rank | P-value: 0.0012

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%

OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented.

Time Frame: Up to approximately 44 months | Units: Months | Type: MEDIAN

Statistical Analyses

• Method: Log Rank | P-value: 0.0013

Secondary Outcomes (8)

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%

PFS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented.

Time Frame: Up to approximately 44 months | Units: Months | Type: MEDIAN

Statistical Analyses

• Method: Log Rank | P-value: 0.0260

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%

PFS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented.

Time Frame: Up to approximately 44 months | Units: Months | Type: MEDIAN

Statistical Analyses

• Method: Log Rank | P-value: 0.2134

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%

PFS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented.

Time Frame: Up to approximately 44 months | Units: Months | Type: MEDIAN

Statistical Analyses

• Method: Log Rank | P-value: 0.7964

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%

ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented.

Time Frame: Up to approximately 44 months | Units: Percentage of participants | Type: NUMBER

Statistical Analyses

• Method: Stratified Miettinen and Nurminen | P-value: 0.0353

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%

ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented.

Time Frame: Up to approximately 44 months | Units: Percentage of participants | Type: NUMBER

Statistical Analyses

• Method: Stratified Miettinen and Nurminen | P-value: 0.0744

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%

ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented.

Time Frame: Up to approximately 44 months | Units: Percentage of participants | Type: NUMBER

Statistical Analyses

• Method: Stratified Miettinen and Nurminen | P-value: 0.4060

Number of Participants Who Experienced At Least One Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.

Time Frame: Up to approximately 38 months | Units: Participants | Type: COUNT_OF_PARTICIPANTS

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.

Time Frame: Up to approximately 35 months | Units: Participants | Type: COUNT_OF_PARTICIPANTS

Adverse Events

Reporting Threshold: 5

Time Frame: Up to approximately 93 months

Population: All participants receiving ≥1 dose of study treatment. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. Therefore, MedDRA preferred terms “Neoplasm progression”, “Malignant neoplasm progression” & “Disease progression” not related to study drug are excluded as AEs.

Event Summary

Serious Adverse Events (258)

Other Adverse Events (46)

Additional Information

PI is Sponsor Employee: No

Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC
• Email: ClinicalTrialsDisclosure@merck.com
• Phone: 1-800-672-6372

IPD Sharing Statement

IPD Sharing: YES

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

URL: http://engagezone.msd.com/ds_documentation.php

Documents & Links

Study Documents

References (5)

• [1] de Castro G Jr, Kudaba I, Wu YL, Lopes G, Kowalski DM, Turna HZ, Caglevic C, Zhang L, Karaszewska B, Laktionov KK, Srimuninnimit V, Bondarenko I, Kubota K, Mukherjee R, Lin J, Souza F, Mok TSK, Cho BC. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non-Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score >/= 1% in the KEYNOTE-042 Study. J Clin Oncol. 2023 Apr 10;41(11):1986-1991. doi: 10.1200/JCO.21.02885. Epub 2022 Oct 28. (PMID: 36306479) [DERIVED]
• [2] Halmos B, Burke T, Kalyvas C, Insinga R, Vandormael K, Frederickson A, Piperdi B. Indirect comparison of pembrolizumab monotherapy versus nivolumab + ipilimumab in first-line metastatic lung cancer. Immunotherapy. 2022 Apr;14(5):295-307. doi: 10.2217/imt-2021-0273. Epub 2022 Jan 25. (PMID: 35073727) [DERIVED]
• [3] Wu YL, Zhang L, Fan Y, Zhou J, Zhang L, Zhou Q, Li W, Hu C, Chen G, Zhang X, Zhou C, Dang T, Sadowski S, Kush DA, Zhou Y, Li B, Mok T. Randomized clinical trial of pembrolizumab vs chemotherapy for previously untreated Chinese patients with PD-L1-positive locally advanced or metastatic non-small-cell lung cancer: KEYNOTE-042 China Study. Int J Cancer. 2021 May 1;148(9):2313-2320. doi: 10.1002/ijc.33399. Epub 2020 Dec 9. (PMID: 33231285) [DERIVED]
• [4] Weng X, Luo S, Lin S, Zhong L, Li M, Xin R, Huang P, Xu X. Cost-Utility Analysis of Pembrolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer With Different PD-L1 Expression Levels. Oncol Res. 2020 Mar 27;28(2):117-125. doi: 10.3727/096504019X15707883083132. Epub 2019 Oct 14. (PMID: 31610828) [DERIVED]
• [5] Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. doi: 10.1016/S0140-6736(18)32409-7. Epub 2019 Apr 4. (PMID: 30955977) [DERIVED]