TOPLINE:

In a meta-analysis of 23 studies, patients with head and neck cancer had a far higher pathologic response rate when they received chemoimmunotherapy before surgery vs immunotherapy alone. Randomized clinical trial evidence on additional outcomes is still needed.

METHODOLOGY:

• Neoadjuvant immunotherapy is an established standard of care prior to surgery in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC). Questions remain, however, about the efficacy of neoadjuvant immunotherapy alone compared with neoadjuvant chemoimmunotherapy.
• To update the current literature, researchers conducted a systematic review of 23 prospective phase 1 and 2 trials involving 751 patients with treatment-naive, resectable HNSCC (77% male; age range, 27-87 years). Prior to surgery, 357 patients received chemoimmunotherapy, 102 received dual-agent immunotherapy, and 292 received single-agent immunotherapy.
• A meta-analysis was performed using a binary random-effects model to determine the pooled proportion of primary outcomes in the immunotherapy and chemoimmunotherapy groups.
• Primary outcomes included major pathologic response (< 10% viable tumor left after resection) and complete pathologic response (no viable tumor after resection). Secondary outcomes included 1-year overall survival and toxicities.

TAKEAWAY:

• Pooled rates of major and complete pathologic response were 66% (95% CI, 58%-73%) for chemoimmunotherapy, 18% (95% CI, 6%-29%) for dual-agent immunotherapy, and 6% (95% CI, 3%-9%) for single-agent immunotherapy. The differences may reflect synergistic effects whereby chemotherapy reduces tumor mass, allowing immunotherapy agents to act more effectively, the authors of the study noted.
• Across the studies, 1-year overall survival rates were similar with all three neoadjuvant regimens — ranging from 88% to 96% for single-agent immunotherapy, 88% to 96% for dual-agent immunotherapy, and 88% to 100% for chemoimmunotherapy.
• Adverse events of grade 3 or higher were reported in 61 of 210 patients (29%) receiving single-agent immunotherapy, 2 of 67 patients (3%) receiving dual-agent immunotherapy, and 36 of 210 patients (17%) receiving chemoimmunotherapy. The most commonly reported adverse events included leukopenia, anemia, neutropenia, colitis, and rash.

IN PRACTICE:

“Evidence from this pooled meta-analysis reporting differential pathologic response rates to neoadjuvant chemoimmunotherapy compared with immunotherapy alone calls for randomized phase 3 trials directly comparing the 2 regimens in HNSCC,” the study authors wrote. An accompanying editorial concurred, noting that “no inference” can be made regarding the impact on patient survival based on current evidence.

“Only through such rigorously designed studies can the incremental value (and appropriate patient population) for neoadjuvant chemoimmunotherapy in curative-intent HNSCC be clearly defined,” wrote Kevin Contrera, MD, University of Pittsburgh Medical Center, Pittsburgh, and colleagues.

SOURCE:

The study, led by Linda X. Yin, MD, Mayo Clinic, Rochester, Minnesota, was published online on March 12 in JAMA Otolaryngology-Head & Neck Surgery.

LIMITATIONS:

Many of the included studies were single-group trials, preventing direct comparison between immunotherapy and chemoimmunotherapy response in the meta-analysis. High heterogeneity was observed in the pooled pathologic response rates across neoadjuvant chemoimmunotherapy trials, suggesting that patient selection and the ability to identify biological responders to systemic therapy using biomarkers will be key in future trials. Most patients had human papillomavirus-negative T3 or T4 disease, which may limit generalizability to other patient populations.

DISCLOSURES:

No funding information was reported. Several authors disclosed serving as industry consultants, and one author reported holding a patent for methylation markers licensed to Exact Sciences. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.