Chemoimmunotherapy Shows Higher Pathologic Response in Head and Neck Cancer

Patients with head and neck cancer had substantially higher pathologic response rates when they received chemoimmunotherapy before surgery compared with immunotherapy alone, according to a meta-analysis of 23 prospective phase 1 and 2 trials. The findings call for randomized phase 3 trials to determine whether the improved pathologic response translates to survival benefits.

The systematic review involved 751 patients with treatment-naive, resectable head and neck squamous cell carcinoma (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.

Pooled rates of major pathologic response (less than 10% viable tumor left after resection) 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. Complete pathologic response rates (no viable tumor after resection) followed similar patterns. The differences may reflect synergistic effects whereby chemotherapy reduces tumor mass, allowing immunotherapy agents to act more effectively.

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.

The study authors noted that 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 two regimens in head and neck squamous cell carcinoma. An accompanying editorial concurred, noting that "no inference" can be made regarding the impact on patient survival based on current evidence.

The editorial authors wrote that only through rigorously designed studies can the incremental value and appropriate patient population for neoadjuvant chemoimmunotherapy in curative-intent head and neck squamous cell carcinoma be clearly defined.

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.

The study was published online on March 12 in JAMA Otolaryngology-Head & Neck Surgery.