Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial.

PURPOSE: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888). METHODS: Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review (BICR), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pembrolizumab 200 mg intravenously once every 3 weeks for ≤35 cycles and carboplatin AUC 5 mg/mL/min intravenously once every 3 weeks for ≤6 cycles and investigator's choice of paclitaxel 100 mg/m2 on days 1 and 8 or 175 mg/m2 on day 1, intravenously once every 3 weeks. The primary end point was objective response rate per RECIST v1.1 by BICR. RESULTS: Between October 27, 2020, and April 29, 2022, 149 patients were screened and 101 received treatment. As of February 20, 2023, the median follow-up was 18.9 months (range, 9.1-27.0). At this final analysis, 49 (49%) of 101 patients had an objective response (95% CI, 38.4 to 58.7), including seven patients (7%) with a confirmed complete response. Of the 101 treated patients, grade 3-5 and serious treatment-related adverse events occurred in 76 (75%) and 27 (27%), respectively. There were no new safety signals. CONCLUSION: Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC, suggesting this combination may be an alternative option for this patient population.

Clinical outcomes and prognostic factors in cisplatin versus cetuximab chemoradiation for locally advanced p16 positive oropharyngeal carcinoma.

OBJECTIVES: Randomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the off-trial use of cetuximab in p16+ patients is increasing, even in those who could potentially tolerate cisplatin. The purpose of this study was to compare the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and to identify prognostic factors and predictors of tumor response. MATERIALS AND METHODS: Cases of p16+ OPC treated with cisplatin or cetuximab CRT at our institution from 2010 to 2014 were identified. Recursive partitioning analysis (RPA) classification was used to determine low-risk (LR-RPA) and intermediate-risk (IR-RPA) groups. Log-rank/Kaplan-Meier and Cox Regression methods were used to compare groups. RESULTS: We identified 205 patients who received cisplatin (n = 137) or cetuximab (n = 68) CRT in the definitive (n = 178) or postoperative (n = 27) setting. Median follow-up was 3 years. Cisplatin improved 3-year locoregional control (LRC) [92.7 vs 65.4%], distant metastasis-free survival (DMFS) [88.3 vs 71.2%], recurrence-free survival (RFS) [86.6 vs 50.6%], and overall survival (OS) [92.6 vs 72.2%] compared to cetuximab [all p < .001]. Concurrent cisplatin improved 3-year OS for LR-RPA (97.1 vs 80.3%, p < .001) and IR-RPA (97.1 vs 80.3%, p < .001) groupings. CONCLUSION: When treating p16+ OPC with CRT, the threshold for substitution of cisplatin with cetuximab should be maintained appropriately high in order to prolong survival times and optimize locoregional and distant tumor control. When cetuximab is used in cisplatin-ineligible patients, altered fractionation RT should be considered in an effort to improve LRC.

Phase II evaluation of docetaxel-modulated capecitabine in previously treated patients with non-small cell lung cancer.

PURPOSE: Based on the preclinical observation of upregulation of thymidine phosphorylase, the last enzymatic step in the conversion of capecitabine to 5-fluorouracil, by docetaxel along with good clinical tolerability of the combination of docetaxel and capecitabine using an optimized schedule in a previous phase I trial, we conducted this phase II study of this combination in patients with refractory or relapsed non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with NSCLC previously treated with at least one platinum- or paclitaxel-based regimen received docetaxel 36 mg/m(2) on days 1, 8, and 15 and capecitabine 625 mg/m(2) twice daily on days 5 to 18, every 4 weeks. The primary objective of the study was evaluation of progression-free survival (PFS) 26 weeks from initiation of treatment. RESULTS: Thirty-six evaluable patients received 104 cycles of the combination. Severe toxicities were infrequent with only one patient requiring toxicity-related hospitalization. The 26-week PFS rate was 25% (95% confidence interval, 12-42) with an intent to treat median survival and 1-year survival rate of 9.1 months and 37%, respectively. Among 31 patients with measurable disease (Response Evaluation Criteria in Solid Tumors criteria), eight (26%; 95% confidence interval, 12-45) achieved partial responses. CONCLUSION: The combination of capecitabine and weekly docetaxel is well tolerated in previously treated patients with NSCLC. The relatively high 26-week PFS and 1-year survival, as well as the high response rate observed, encourages further evaluation of this regimen in NSCLC, either in randomized trials for refractory patients or as a potential treatment option for chemotherapy naive patients.