Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer
| Autor: | Heather Crowe, Susan Schumer, Elizabeth H. Stover, Jennifer Curtis, Ursula A. Matulonis, Jeffrey J. Ishizuka, Alexi A. Wright, Neal I. Lindeman, Christin Whalen, Mary K. Buss, Whitfield B. Growdon, Sarah J. Hill, Roxanne Quinn, Carolyn N. Krasner, Allison Gockley, Stephen A. Cannistra, Doga Gulhan, Gini F. Fleming, Kathryn P. Gray, Weixiu Luo, Joyce F. Liu, Richard T. Penson, Panagiotis A. Konstantinopoulos, Susana M. Campos |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Pembrolizumab Antibodies Monoclonal Humanized DNA Mismatch Repair Cohort Studies Avelumab 03 medical and health sciences 0302 clinical medicine medicine Humans Progression-free survival business.industry Endometrial cancer Antibodies Monoclonal ORIGINAL REPORTS medicine.disease Progression-Free Survival Immune checkpoint Endometrial Neoplasms Blockade Clinical trial 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Female DNA mismatch repair business medicine.drug |
| Zdroj: | J Clin Oncol |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.19.01021 |
| Popis: | PURPOSE Despite the tissue-agnostic approval of pembrolizumab in mismatch repair deficient (MMRD) solid tumors, important unanswered questions remain about the role of immune checkpoint blockade in mismatch repair–proficient (MMRP) and –deficient endometrial cancer (EC). METHODS This phase II study evaluated the PD-L1 inhibitor avelumab in two cohorts of patients with EC: (1) MMRD/ POLE (polymerase ε) cohort, as defined by immunohistochemical (IHC) loss of expression of one or more mismatch repair (MMR) proteins and/or documented mutation in the exonuclease domain of POLE; and (2) MMRP cohort with normal IHC expression of all MMR proteins. Coprimary end points were objective response (OR) and progression-free survival at 6 months (PFS6). Avelumab 10 mg/kg intravenously was administered every 2 weeks until progression or unacceptable toxicity. RESULTS Thirty-three patients were enrolled. No patient with POLE-mutated tumor was enrolled in the MMRD cohort, and all MMRP tumors were not POLE-mutated. The MMRP cohort was closed at the first stage because of futility: Only one of 16 patients exhibited both OR and PFS6 responses. The MMRD cohort met the predefined primary end point of four ORs after accrual of only 17 patients; of 15 patients who initiated avelumab, four exhibited OR (one complete response, three partial responses; OR rate, 26.7%; 95% CI, 7.8% to 55.1%) and six (including all four ORs) PFS6 responses (PFS6, 40.0%; 95% CI, 16.3% to 66.7%), four of which are ongoing as of data cutoff date. Responses were observed in the absence of PD-L1 expression. IHC captured all cases of MMRD subsequently determined by polymerase chain reaction or genomically via targeted sequencing. CONCLUSION Avelumab exhibited promising activity in MMRD EC regardless of PD-L1 status. IHC for MMR assessment is a useful tool for patient selection. The activity of avelumab in MMRP/non- POLE–mutated ECs was low. |
| Databáze: | OpenAIRE |
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