Interventional Trials in Metastatic Head and Neck SCC (CT, public)

Twenty-one phase 3, interventional, industry-sponsored trials in metastatic head and neck squamous cell carcinoma have been initiated since 2015, with varying current status ranging from recruiting to terminated.

Abstract

Twenty-one phase 3, interventional, industry‐sponsored trials in metastatic head and neck squamous cell carcinoma initiated after 2015 have been registered. Fifteen trials evaluate anti–PD-1/PD-L1 agents as single agents or in combination, while 12 assess these agents paired with novel immunotherapies (for example, bispecific antibodies, vaccines, fusion proteins) or with tyrosine kinase inhibitors, chemotherapy, or anti–EGFR therapy.

Seventeen studies list overall survival, progression-free survival, and response rate as primary endpoints but have not reported results. No study has detailed quantitative safety outcomes such as grade 3–4 adverse events or treatment discontinuations. Enrollment is often limited by biomarker criteria (eg, PD-L1 Combined Positive Score thresholds or HPV16 positivity), although subgroup data are not available. Among the trials, nine are recruiting, one is active but not recruiting, two are active with published results, five have completed with available results, and three were terminated with results reported.

Methods

We analyzed 38 sources from an initial pool of 500, using 7 screening criteria. Each paper was reviewed for 5 key aspects that mattered most to the research question. More on methods

Papers identified with Elicit search

• n = 500

Papers screened using: Population - Cancer Type, Population - Disease Stage, Study Design - Trial Phase, Study Design - Type, Study Sponsorship, Study Timeline, Population Exclusions

• Papers screened out
• n = 462

Papers included for extraction

• n = 38

Screening

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

• Population - Cancer Type: Does the study specifically focus on patients with squamous cell carcinoma of head and neck (HNSCC)?
• Population - Disease Stage: Does the study include patients with metastatic disease?
• Study Design - Trial Phase: Is this a Phase 3 clinical trial?
• Study Design - Type: Is this an interventional study?
• Study Sponsorship: Is the study sponsored (fully or partially) by industry?
• Study Timeline: Did the study start on or after January 1, 2015?
• Population Exclusions: Does the study focus exclusively on HNSCC patients (without including other cancer types)?

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 Type and Phase:

Extract the specific study type (e.g., interventional) and exact phase (e.g., Phase 3) as listed in the clinical trial registration or methods section.

Sponsorship Details:

Identify the primary sponsor of the study.

Participant Eligibility Criteria:

Extract key inclusion and exclusion criteria specific to:

• Disease stage (metastatic squamous cell carcinoma)
• Age range
• Performance status
• Prior treatments

Geographical Locations:

List all countries where the study is being conducted.

Primary Intervention:

Describe the primary intervention in detail:

• Specific drugs/treatments used
• Combination therapies
• Dosage (if specified)
• Administration method

Results

Characteristics of Included Studies

Summary of intervention types:

• Anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) agents: Found in 15 studies, either alone or in combination.
• Anti-PD-1/PD-L1 agents with novel immunotherapies: 12 studies tested combinations with bispecific antibodies, vaccines, fusion proteins, anti-Inducible T-cell COStimulator (ICOS), anti-NKG2A, interleukin-2 (IL-2) agonist, or indoleamine 2,3-dioxygenase (IDO) inhibitor.

Summary of trial status:

• 9 studies were recruiting.
• 1 study was active, not recruiting.
• 2 studies were active, not recruiting, with results available.
• 5 studies were completed, with results available.
• 3 studies were terminated, with results available.

Summary of primary endpoints:

• 17 studies listed efficacy and safety as primary endpoints.

Effects

Primary Outcomes

Summary of findings:

• For Overall Survival:
  • 17 studies had not yet reported results.
• For Progression-Free Survival:
  • 17 studies had not yet reported results.

Safety and Tolerability

Summary of findings:

• For 17 studies, we found “No mention found” for all three safety outcomes.

Subgroup Analyses

Biomarker-Based Outcomes

• We didn’t find mention of biomarker-based efficacy or safety outcomes in the extracted data.

Regional Variations

• Most industry-sponsored studies are global, with sites in North America, Europe, Asia, and South America.

Discussion

• We identified a large number of phase 3, interventional, industry-sponsored trials in metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) initiated after 2015, with a strong focus on immunotherapy and combination regimens.
• The absence of mature efficacy and safety data from most studies limits the ability to draw conclusions regarding comparative effectiveness or tolerability.

References

1. Study of Dostarlimab vs Placebo
2. Single-agent Capecitabine as Metronomic Chemotherapy
3. Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab