Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study

Abstract

There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti-programmed death 1 receptor antibody, in this platinum-and cetuximabpretreated population with poor prognosis. MethodsEligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. Primary end points: overall response rate (Response Evaluation Criteria in Solid Tumors v1.1, central review) and safety. Efficacy was assessed in all dosed patients and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status. ResultsAmong 171 patients treated, 75% received two or more prior lines of therapy for metastatic disease, 82% were PD-L1 positive, and 22% were HPV positive. At the time of analysis, 109 patients (64%) experienced a treatment-related adverse event; 26 patients (15%) experienced a grade $ 3 event.Seven patients (4%) discontinued treatment, and one died of treatment-related adverse events. Overall response rate was 16% (95% CI, 11% to 23%), with a median duration of response of 8 months (range, 2+ to 12+ months); 75% of responses were ongoing at the time of analysis. Response rates were similar in all HPV and PD-L1 subgroups. Median progression-free survival was 2.1 months, and median overall survival was 8 months. ConclusionPembrolizumab exhibited clinically meaningful antitumor activity and an acceptable safety profile in recurrent/metastatic head and neck squamous cell carcinoma previously treated with platinum and cetuximab.J Clin Oncol 35:1542-1549.

Association between pretreatment lymphocyte count and response to PD1 inhibitors in head and neck squamous cell carcinomas

“…Patients in the lower ALC group had median PFS of 2 months, which mirrored those of previous studies [17–19]. Interestingly, in the higher ALC group, the median PFS was approximately 5 months.…”

“…Also, the current cohort represented a relatively more treatment-naïve group of patients as suggested by the apparently higher ORR and longer overall PFS compared to previous studies [17–19]. Another limitation may be the inclusion of some patients with nasopharyngeal carcinoma (NPC), which was not included in landmark trials that have led to the approval of anti-PD1 antibodies in HNSCC; the use of pembrolizumab in NPCs is currently a category 2B recommendation based on the latest update of the National Comprehensive Cancer Network guidelines [2].…”

Checkpoint Inhibitors in Head and Neck Cancer: Current Knowledge and Perspectives

“…Based on these findings, the Food and Drug Administration (FDA) granted pembrolizumab accelerated approval in August 2016 for patients with R/M HNSCC with disease progression on, or after, platinum-containing chemotherapy. Recently, KEYNOTE-055, a phase II single-arm study, evaluated pembrolizumab in 171 patients with R/M HNSCC refractory to platinum and cetuximab 18. Median age was 61 and three-quarters of patients had received at least two prior therapies.…”

“…The 6-month OS rate was also higher for HPV-positive (70% vs 56%). In the phase II KEYNOTE-055 trial evaluating pembrolizumab in R/M HNSCC refractory to platinum and cetuximab, response rates were similar irrespective of HPV status (16%) but OS at 6 months was higher in HPV-associated disease (72% vs 55% in HPV-negative disease) 18. On the other hand, responses were higher based on PD-L1 status (18% in PD-L1≥1%, 12% in PD-L1<1% and 27% in PD-L1≥50%).…”

The evolutionary nature of the cancer immunotherapy revolution

“…Inhibition of this interaction leads to effective infiltration of activated T cells and ultimately tumor destruction [11]. Remarkably, monoclonal antibodies against PD-1 (pembrolizumab, nivolumab) and PD-L1 (atezolizumab, avelumab, durvalumab) have received regulatory approval in a number of diseases, including melanoma, non-small-cell lung cancer (NSCLC), urothelial bladder cancer (UBC), head and neck squamous cell carcinoma (HNSCC), classical Hodgkin lymphoma and Merkel cell carcinoma, and have shown activity in many others [12][13][14][15][16][17][18][19][20][21]. Building upon this work, data with combination therapy with anti-PD-1/ PD-L1 agents with anticytotoxic T lymphocyte associated antigen 4 (CTLA4) agents, such as ipilimumab, which was FDA-approved as a single agent in metastatic melanoma in 2011, and tremelimumab, is associated with higher response rates in a number of diseases [22][23][24][25][26][27][28].…”