Phase II study of pembrolizumab efficacy and safety in women with recurrent small cell neuroendocrine carcinoma of the lower genital tract

Abstract

Objective: To investigate the efficacy and safety of pembrolizumab in women with recurrent small cell neuroendocrine tumors of the lower genital tract.

Methods: We conducted an open-label, investigator-initiated phase II basket trial of pembrolizumab 200 mg intravenously every 3 weeks in patients with rare tumors (ClinicalTrials.gov: NCT02721732). The trial had prespecified cohorts, including small cell malignancies of extrapulmonary origin. Eligibility criteria included disease progression during standard treatment in the 6 months before study enrollment. Patients were enrolled from February 2017 to February 2019. The primary endpoint was the proportion of patients alive without progression at 27 weeks. Response to pembrolizumab was evaluated every 9 weeks (3 cycles) with radiographic imaging.

Results: Seven women with gynecologic extrapulmonary small cell carcinoma were enrolled, 6 with cervical and 1 with vulvar carcinoma. No patient was progression free at 27 weeks. At first radiologic assessment, 1 patient had stable disease, while 6 had progression. The single patient with stable disease at 6 weeks had disease progression at 14 weeks. The median progression-free interval was 2.1 months (range 0.8-3.3 months). Severe treatment-related adverse events (≥grade 3) were seen in 2 of 7 patients (29%); 1 patient had grade 3 asymptomatic elevation of serum alkaline phosphatase, and 1 had grade 3 asymptomatic elevation of serum alanine aminotransferase.

Conclusions: Pembrolizumab alone showed minimal activity in women with recurrent small cell neuroendocrine tumors of the lower genital tract. Treatment was well tolerated in the majority of study participants, and the rate of severe adverse events was low.

Keywords: Cervical cancer; Checkpoint inhibitor; Immunotherapy; Neuroendocrine; Phase II; Small cell.

Conflict of interest statement

Declaration of competing interest Dr. Frumovitz reports personal fees from Stryker, grants and non-financial support from Astra Zeneca, personal fees from Biom'Up, outside the submitted work. Dr. Jazaeri reports personal fees from Iovance Advisory Board Meeting, Nuprobe, Simcere, Pact Pharma; grants from Astra Zeneca, BMS, Iovance, Aravive, Pfizer, Immatics USA, Eli Lilly, and non-financial support from Astra Zeneca, outside the submitted work. Dr. Karp reports other from Phosplatin Pharmaceutical Co., personal fees from Black Beret Life Sciences, other from AFFIGEN (Immunotherapy Startup Firm), grants from NIH Clinical Translational Science Award Grant, outside the submitted work. Dr. Naing reports other from NCI, other from EMD Serono, other from MedImmune, other from Healios Onc. Nutrition; other from Atterocor, other from Amplimmune, other from ARMO BioSciences, other from Eli Lilly, other from KaryopharmTherapeutics, other from Incyte, other from Novartis, other from Regeneron, other from Merck, other from BMS, other from Pfizer, other from CytomX Therapeutics, other from Neon Therapeutics, other from Calithera Biosciences, other from TopAlliance Biosciences, other from Kymab, other from PsiOxus, other from Immune Deficiency Foundation, other from Genome, outside the submitted work. Dr. Rodon Ahnert reports personal fees and other from Novartis, personal fees from Eli Lilly, personal fees from Orion Pharmaceuticals, personal fees from Peptomyc, personal fees and other from Kelun Pharmaceuticals/Klus Pharma, personal fees and other from Spectrum Pharmaceuticals Inc., personal fees and other from Pfizer, personal fees from Roche Pharmaceuticals, personal fees from Ellipses Pharma, personal fees from Certera, personal fees and other from Bayer, personal fees from Ionctura SA, other from European Journal of Cancer, other from VHIO/Ministero De Empleo Y Seguridad Social, other from Chinese University of Hong Kong, other from SOLTI, other from Elsevier, other from GLAXOSMITHKLINE, other from ESMO, from Department of Defense, other from Merck Sharp & Dohme, other from Lousiania State University, other from Huntsman Cancer Institute, other from Cancer Core Europe, other from Karolinska Cancer Institute, other from King Abdullah International Medical Research Center, other from WIN Consortium, other from Janssen, other from Tocagen, other from Symphogen, other from BioAlta, other from GenMab, other from CytomX, other from Kelun-Biotech, other from Takea-Millenium, other from Ipsen, outside the submitted work. Dr. Westin reports grants and personal fees from AstraZeneca, grants and personal fees from Clovis Oncology, grants and personal fees from GSK/Tesaro, grants and personal fees from Roche/Genentech, grants and personal fees from Novartis, grants from Cotinga Pharmaceuticals, grants from ArQule, grants from Bayer, personal fees from Merck, personal fees from Pfizer, personal fees from Eisai, personal fees from Circulogene, outside the submitted work. Dr. Yap reports grants, personal fees and non-financial support from Merck, outside the submitted work. Drs. Abonofal, Salvo, Xu and Zarifa have nothing to disclose.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Figure 1:

Waterfall plot illustrating response to pembrolizumab in 5 evaluable patients with cervical cancer. Two patients (1 with vulvar cancer and 1 with cervical cancer) had clinical progression before first imaging assessment and are not included in this figure.

Figure 2:

Time to and duration of response to pembrolizumab in 7 evaluable patients