Randomized Phase II Trial of Nivolumab With Stereotactic Body Radiotherapy Versus Nivolumab Alone in Metastatic Head and Neck Squamous Cell Carcinoma.

PURPOSE: The objective response rate (ORR) for single-agent anti-programmed death receptor 1 (anti-PD-1) therapy is modest in patients with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). We aimed to test whether radiotherapy may act synergistically with anti-PD-1 therapy to improve response through the abscopal effect. PATIENTS AND METHODS: We conducted a single-center, randomized, phase II trial of nivolumab (anti-PD-1 therapy) versus nivolumab plus stereotactic body radiotherapy (SBRT) in patients with metastatic HNSCC. Patients had at least two metastatic lesions: one that could be safely irradiated and one measurable by RECIST version 1.1. Patients were randomly assigned (1:1), stratified by human papillomavirus status, to nivolumab (3 mg/kg intravenously every 2 weeks) or nivolumab (same dose) plus SBRT (9 Gy × 3) to 1 lesion. The primary end point was ORR in nonirradiated lesions, which was assessed by RECIST in patients with at least one available set of on-treatment images; safety was assessed in a per-protocol population. RESULTS: Between March 11, 2016, and June 22, 2018, 62 patients were randomly assigned to nivolumab (n = 30) or nivolumab plus SBRT (n = 32). There was no statistically significant ORR difference between arms (34.5% [95% CI, 19.9% to 52.7%] v 29.0% [95% CI, 16.1% to 46.6%]; P = .86). There was no significant difference in overall survival (P = .75), progression-free survival (P = .79), or response duration (P = .26). Grade 3-5 toxicities were similar (13.3% v 9.7%; P = .70). CONCLUSION: We found no improvement in response and no evidence of an abscopal effect with the addition of SBRT to nivolumab in unselected patients with metastatic HNSCC.

Everolimus plus bevacizumab is an effective first-line treatment for patients with advanced papillary variant renal cell carcinoma: Final results from a phase II trial.

BACKGROUND: We previously reported on a phase 2 study of everolimus plus bevacizumab across various nonclear cell renal cell carcinoma (nccRCC) histologies and observed encouraging activity among patients with papillary RCC (pRCC) and unclassified RCC (uRCC) with a major papillary component. We subsequently expanded the study to enroll additional patients with pRCC variants. METHODS: Everolimus plus bevacizumab was administered at standard doses until disease progression or intolerance to therapy. The primary endpoint was the 6-month progression-free survival (PFS) rate; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Correlative analyses included next-generation sequencing (NGS) from tumor and germline across >341 genes of interest. RESULTS: In addition to 19 patients with pRCC variants in the original cohort, 20 patients with similar features were enrolled on the expansion cohort (uRCC with papillary features [n = 24], pRCC [n = 14], and translocation-associated RCC with papillary features [n = 1]). Among 37 evaluable patients, the 6-month PFS rate was 78%, the median PFS was 13.7 months (95% CI, 10.8-16.4 months), and the ORR was 35%. With a median follow-up of 17.6 months, the median OS was 33.9 months (95% CI, 23.3-71.9). Tolerance was consistent with prior reports for everolimus plus bevacizumab. NGS results (n = 33) identified responses in patients with a wide spectrum of genomic alterations, including ARID1A, FH, and MET mutations. CONCLUSION: The expansion cohort results confirm robust activity of everolimus plus bevacizumab in metastatic pRCC variants, supporting this regimen as a standard option for this patient population.