Pembrolizumab alone and pembrolizumab plus chemotherapy in previously treated, extrapulmonary poorly differentiated neuroendocrine carcinomas Journal Article
| Authors: | Raj, N.; Chan, J. A.; Wang, S. J.; Aggarwal, R. R.; Calabrese, S.; DeMore, A.; Fong, L.; Grabowsky, J.; Hope, T. A.; Kolli, K. P.; Mulvey, C. K.; Munster, P. N.; Perez, K.; Punn, S.; Reidy-Lagunes, D.; Von Fedak, S.; Zhang, L.; Bergsland, E. K. |
| Article Title: | Pembrolizumab alone and pembrolizumab plus chemotherapy in previously treated, extrapulmonary poorly differentiated neuroendocrine carcinomas |
| Abstract: | Background: To date, single-agent immune checkpoint inhibitor (CPI) therapy has proven to be ineffective against biomarker-unselected extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PDNECs). The efficacy of CPI in combination with chemotherapy remains under investigation. Methods: Patients with advanced, progressive EP-PDNECs were enrolled in a two-part study of pembrolizumab-based therapy. In Part A, patients received pembrolizumab alone. In Part B, patients received pembrolizumab plus chemotherapy. Primary endpoint: objective response rate (ORR). Secondary endpoints: safety, progression-free survival (PFS) and overall survival (OS). Tumours were profiled for programmed death-ligand 1 expression, microsatellite-high/mismatch repair deficient status, mutational burden (TMB), genomic correlates. Tumour growth rate was evaluated. Results: Part A (N = 14): ORR (pembrolizumab alone) 7% (95% CI, 0.2–33.9%), median PFS 1.8 months (95% CI, 1.7–21.4), median OS 7.8 months (95% CI, 3.1–not reached); 14% of patients (N = 2) had grade 3/4 treatment-related adverse events (TRAEs). Part B (N = 22): ORR (pembrolizumab plus chemotherapy) 5% (95% CI, 0–22.8%), median PFS 2.0 months (95% CI, 1.9–3.4), median OS 4.8 months (95% CI, 4.1–8.2); 45% of patients (N = 10) had grade 3/4 TRAEs. The two patients with objective response had high-TMB tumours. Discussion: Treatment with pembrolizumab alone and pembrolizumab plus chemotherapy was ineffective in advanced, progressive EP-PDNECs. Clinical trial registration: ClinicalTrials.gov NCT03136055. © 2023, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | adult; cancer chemotherapy; cancer survival; clinical article; controlled study; human tissue; protein expression; treatment response; aged; overall survival; genetics; clinical trial; constipation; fatigue; neutropenia; advanced cancer; cancer growth; diarrhea; drug efficacy; drug safety; gastrointestinal hemorrhage; side effect; paclitaxel; cancer patient; antineoplastic agent; anorexia; cancer immunotherapy; metastasis; progression free survival; antineoplastic metal complex; multiple cycle treatment; pain; phase 2 clinical trial; sensory neuropathy; anemia; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; dehydration; creatinine; irinotecan; monoclonal antibody; arthralgia; chill; fever; lymphocytopenia; neuroendocrine tumor; pneumonia; pruritus; rash; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; hyponatremia; multicenter study; mismatch repair; microsatellite instability; muscle weakness; open study; heartburn; headache; leukocyte count; liver function test; memory disorder; gastroesophageal reflux; dry eye; dry skin; epistaxis; neuroendocrine tumors; neuroendocrine carcinoma; carcinoma, neuroendocrine; growth rate; hoarseness; programmed death 1 ligand 1; progression-free survival; bloating; clinical outcome; overall response rate; body weight loss; antibodies, monoclonal, humanized; combination drug therapy; infusion related reaction; humans; human; male; female; article; pembrolizumab; median survival time; tumor mutational burden; extrapulmonary poorly differentiated neuroendocrine carcinoma |
| Journal Title: | British Journal of Cancer |
| Volume: | 129 |
| Issue: | 2 |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-08-10 |
| Start Page: | 291 |
| End Page: | 300 |
| Language: | English |
| DOI: | 10.1038/s41416-023-02298-8 |
| PUBMED: | 37208512 |
| PROVIDER: | scopus |
| PMCID: | PMC10338510 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Nitya Raj -- Source: Scopus |
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