3566 - Pembrolizumab in Advanced Rare Cancers

Background

Patients with rare cancers account for 25% of cancer-related deaths but have limited treatment options. As immunotherapy has potential applicability across cancer types, we conducted an open-label phase II trial of pembrolizumab in patients with advanced rare cancers.

Methods

Eligible patients who had progressed on standard therapies in the last 6 months were enrolled in 9 tumor-specific cohorts and in a 10th cohort for other histologies. Pembrolizumab 200 mg every 3 weeks was administered for 2 years or until disease progression or intolerable toxicity. Tumor imaging was performed every 9 weeks; response was assessed by RECIST v1.1 and irRECIST. Adverse events (AEs) were graded per NCI-CTCAE v4.03.

Results

A total of 127 patients with advanced rare cancer were treated. Median age = 56 years and median number of prior therapies = 2. At data cutoff date, the non-progression rate (NPR) at 27 weeks was 28%, ORR 14% (immune-related [ir] complete response [irCR] = 1 and partial response [irPR] = 14, 11 continuing therapy at data cut-off), and clinical benefit rate (CBR; irCR + irPR + ir stable disease ≥4 months) 38%. In the squamous cell carcinoma (SCC) of the skin cohort, NPR at 27 weeks was 36%, ORR 31% (5 of 16 evaluable; irCR = 1 and irPR = 4, 4 continuing therapy), and CBR 38%. In the adrenocortical carcinoma (ACC) cohort, NPR at 27 weeks was 31%, ORR 15% (2 of 13 evaluable; irPR = 2), and CBR 54%. In the carcinoma of unknown primary (CUP) cohort, NPR at 27 weeks was 33%, ORR 23% (3 of 13 evaluable; irPR = 3, all continuing therapy), and CBR 54%. In the paraganglioma-pheochromocytoma cohort, NPR at 27 weeks was 43% and CBR 75% (6 of 8 evaluable). A higher proportion of patients with baseline PD-L1 H-score >42.5 were alive and progression free at 27 weeks (47%, vs 20% for H-score ≤ 42.5; p = 0.02). During the study, 66 (52%) patients had drug-related AEs, 12 (9%) with grade ≥3 AEs. irAEs were observed in 20% of patients. The most common AEs were fatigue (n = 25) and rash (n = 17) and irAEs were hypothyroidism (n = 14), pneumonitis (n = 4) and hyperthyroidism (n = 4). There were 6 deaths during the study, 5 due to progressive disease and 1 due to acute kidney injury secondary to sepsis.

Conclusions

Toxicity with pembrolizumab was manageable and antitumor activity was observed in patients with SCC of skin, ACC, CUP, and paraganglioma-pheochromocytoma.

Clinical trial identification

NCT02721732.

Editorial acknowledgement

Legal entity responsible for the study

Aung Naing, MD.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Disclosure

All authors have declared no conflicts of interest.