Lenvatinib plus pembrolizumab in Japanese patients with endometrial cancer: Results from Study 309/KEYNOTE-775 Journal Article
| Authors: | Yonemori, K.; Yunokawa, M.; Ushijima, K.; Sakata, J.; Shikama, A.; Minobe, S.; Usami, T.; Enomoto, T.; Takehara, K.; Hasegawa, K.; Yamagami, W.; Yamamoto, K.; Han, S.; Dutta, L.; Orlowski, R.; Miura, T.; Makker, V.; Fujiwara, K. |
| Article Title: | Lenvatinib plus pembrolizumab in Japanese patients with endometrial cancer: Results from Study 309/KEYNOTE-775 |
| Abstract: | Study 309/KEYNOTE-775 is a phase 3 open-label, randomized trial of lenvatinib plus pembrolizumab versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer with progression after platinum-based therapy. Primary endpoints of superiority for lenvatinib plus pembrolizumab were met for progression-free survival (PFS) and overall survival (OS) in all-comers (ie, regardless of mismatch repair [MMR] status) and patients with MMR proficiency (pMMR). We present results for the Japanese subset. Patients were randomized to oral lenvatinib 20 mg/day plus intravenous pembrolizumab 200 mg every 3 weeks (Q3W; up to 35 cycles of pembrolizumab) or TPC (intravenous doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 QW [3 weeks on/1 week off]). Primary endpoints were PFS by blinded independent central review per RECIST version 1.1 and OS. One hundred four patients were randomized in Japan (data cutoff, October 26, 2020; median follow-up, 11.8 [range, 1.1–26.9] months). Hazard ratios (HRs) for PFS with lenvatinib plus pembrolizumab versus TPC were 1.04 (95% CI, 0.63–1.73) in patients with pMMR and 0.81 (0.50–1.31) in all-comers. Hazard ratios for OS were 0.74 (0.41–1.34) with pMMR and 0.59 (0.33–1.04) for all-comers. Adverse events were manageable and led to discontinuation of one/both study drugs in 36.5% of patients in the lenvatinib plus pembrolizumab group versus 7.8% in the TPC group. Similar to the global Study 309/KEYNOTE-775 results, this analysis suggested favorable efficacy and manageable safety with lenvatinib plus pembrolizumab after platinum-based chemotherapy in Japanese patients with advanced endometrial cancer and supports this combination as a new standard of care in this population. © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. |
| Keywords: | adult; controlled study; human tissue; treatment response; aged; survival analysis; major clinical study; overall survival; doxorubicin; cancer combination chemotherapy; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; paclitaxel; cancer patient; outcome assessment; follow up; endometrial cancer; antineoplastic agent; endometrial neoplasms; endometrium cancer; carboplatin; progression free survival; antineoplastic metal complex; multiple cycle treatment; neutrophil count; anemia; nausea; randomized controlled trial; stomatitis; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; myalgia; monoclonal antibody; alanine aminotransferase blood level; arthralgia; drug hypersensitivity; fever; alanine aminotransferase; malaise; heart failure; mismatch repair; cardiotoxicity; headache; leukocyte count; hyperthyroidism; hypothyroidism; hand foot syndrome; alopecia; japan; protein msh6; endometrium tumor; proteinuria; mismatch repair protein pms2; cardiomyopathy; treatment outcomes; randomized controlled trial (topic); decreased appetite; phase 3 clinical trial (topic); comparative effectiveness; quinolines; quinoline derivative; clinical outcome; multicenter study (topic); cancer prognosis; response evaluation criteria in solid tumors; antibodies, monoclonal, humanized; body weight disorder; infusion related reaction; phenylurea compounds; lenvatinib; carbanilamide derivative; intention to treat analysis; humans; human; female; article; pembrolizumab; median survival time; treatment interruption; japanese (people); mutl protein homolog 1; dna mismatch repair protein msh2; treatment response time |
| Journal Title: | Cancer Science |
| Volume: | 113 |
| Issue: | 10 |
| ISSN: | 1347-9032 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2022-10-01 |
| Start Page: | 3489 |
| End Page: | 3497 |
| Language: | English |
| DOI: | 10.1111/cas.15436 |
| PUBMED: | 35612971 |
| PROVIDER: | scopus |
| PMCID: | PMC9530883 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2022 -- Source: Scopus |
