Jhanelle E Gray, Michael Schenker, Mehmet Ali Nahit Şendur, Viktoriya Leonova, Dariusz Kowalski, Terufumi Kato, Rashida Orlova, James Chih-Hsin Yang, Adrian Langleben, Arnold Pilz, Andrei Ungureanu, Milena Perez Mak, Flavia De Angelis, Himani Aggarwal, Zachary Zimmer, Bin Zhao, Mark Shamoun, Tae Min Kim
{"title":"Pembrolizumab联合Olaparib与Pembrolizumab联合培美曲塞作为转移性非鳞状非小细胞肺癌维持疗法的3期KEYLYNK-006研究。","authors":"Jhanelle E Gray, Michael Schenker, Mehmet Ali Nahit Şendur, Viktoriya Leonova, Dariusz Kowalski, Terufumi Kato, Rashida Orlova, James Chih-Hsin Yang, Adrian Langleben, Arnold Pilz, Andrei Ungureanu, Milena Perez Mak, Flavia De Angelis, Himani Aggarwal, Zachary Zimmer, Bin Zhao, Mark Shamoun, Tae Min Kim","doi":"10.1016/j.jtho.2024.10.026","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Poly (ADP-ribose) inhibitors, including olaparib, upregulate programmed cell death ligand 1 (PD-L1), which may increase efficacy of anti-PD-(L)1 therapies.</p><p><strong>Methods: </strong>In the phase 3 KEYLYNK-006 trial (NCT03976323), eligible adults with previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations who had complete response (CR), partial response (PR), or stable disease (SD) following induction therapy with 4 cycles of pembrolizumab 200 mg Q3W, pemetrexed 500 mg/m<sup>2</sup> , and carboplatin AUC5 or cisplatin 75 mg/m<sup>2</sup> were randomized 1:1 to olaparib 300 mg orally twice daily or pemetrexed Q3W, both given with ≤31 cycles of pembrolizumab Q3W. Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). PFS was tested at interim analysis 2 (IA2; ie, final PFS analysis), OS at final analysis (FA).</p><p><strong>Results: </strong>Of 1003 patients who received induction therapy, 672 (67.0%) were randomized to pembrolizumab plus olaparib (n=337) or pembrolizumab plus pemetrexed (n=335) in the intention-to-treat population. Median follow-up at FA was 39.9 (range, 28.1-51.5) months. At IA2, median (95% CI) PFS was 7.1 (5.6-8.7) months versus 8.3 (6.9-11.5) months in the olaparib versus pemetrexed groups (HR, 1.12; 95% CI, 0.92-1.36; P=0.87). At FA, median (95% CI) OS was 20.7 (18.0-24.8) months versus 23.0 (19.0-26.4) months (HR, 1.04; 95% CI, 0.87-1.25; P=0.6649). Grade 3-5 maintenance treatment-related AEs occurred in 26.1% versus 30.1% patients.</p><p><strong>Conclusion: </strong>Pembrolizumab plus maintenance olaparib did not improve PFS or OS versus pembrolizumab plus pemetrexed in previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0000,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Phase 3 KEYLYNK-006 Study of Pembrolizumab plus Olaparib versus Pembrolizumab plus Pemetrexed as Maintenance Therapy for Metastatic Nonsquamous Non-Small-Cell Lung Cancer.\",\"authors\":\"Jhanelle E Gray, Michael Schenker, Mehmet Ali Nahit Şendur, Viktoriya Leonova, Dariusz Kowalski, Terufumi Kato, Rashida Orlova, James Chih-Hsin Yang, Adrian Langleben, Arnold Pilz, Andrei Ungureanu, Milena Perez Mak, Flavia De Angelis, Himani Aggarwal, Zachary Zimmer, Bin Zhao, Mark Shamoun, Tae Min Kim\",\"doi\":\"10.1016/j.jtho.2024.10.026\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Poly (ADP-ribose) inhibitors, including olaparib, upregulate programmed cell death ligand 1 (PD-L1), which may increase efficacy of anti-PD-(L)1 therapies.</p><p><strong>Methods: </strong>In the phase 3 KEYLYNK-006 trial (NCT03976323), eligible adults with previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations who had complete response (CR), partial response (PR), or stable disease (SD) following induction therapy with 4 cycles of pembrolizumab 200 mg Q3W, pemetrexed 500 mg/m<sup>2</sup> , and carboplatin AUC5 or cisplatin 75 mg/m<sup>2</sup> were randomized 1:1 to olaparib 300 mg orally twice daily or pemetrexed Q3W, both given with ≤31 cycles of pembrolizumab Q3W. Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). PFS was tested at interim analysis 2 (IA2; ie, final PFS analysis), OS at final analysis (FA).</p><p><strong>Results: </strong>Of 1003 patients who received induction therapy, 672 (67.0%) were randomized to pembrolizumab plus olaparib (n=337) or pembrolizumab plus pemetrexed (n=335) in the intention-to-treat population. Median follow-up at FA was 39.9 (range, 28.1-51.5) months. At IA2, median (95% CI) PFS was 7.1 (5.6-8.7) months versus 8.3 (6.9-11.5) months in the olaparib versus pemetrexed groups (HR, 1.12; 95% CI, 0.92-1.36; P=0.87). At FA, median (95% CI) OS was 20.7 (18.0-24.8) months versus 23.0 (19.0-26.4) months (HR, 1.04; 95% CI, 0.87-1.25; P=0.6649). Grade 3-5 maintenance treatment-related AEs occurred in 26.1% versus 30.1% patients.</p><p><strong>Conclusion: </strong>Pembrolizumab plus maintenance olaparib did not improve PFS or OS versus pembrolizumab plus pemetrexed in previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations.</p>\",\"PeriodicalId\":17515,\"journal\":{\"name\":\"Journal of Thoracic Oncology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":21.0000,\"publicationDate\":\"2024-11-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Thoracic Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jtho.2024.10.026\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thoracic Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jtho.2024.10.026","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
The Phase 3 KEYLYNK-006 Study of Pembrolizumab plus Olaparib versus Pembrolizumab plus Pemetrexed as Maintenance Therapy for Metastatic Nonsquamous Non-Small-Cell Lung Cancer.
Background: Poly (ADP-ribose) inhibitors, including olaparib, upregulate programmed cell death ligand 1 (PD-L1), which may increase efficacy of anti-PD-(L)1 therapies.
Methods: In the phase 3 KEYLYNK-006 trial (NCT03976323), eligible adults with previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations who had complete response (CR), partial response (PR), or stable disease (SD) following induction therapy with 4 cycles of pembrolizumab 200 mg Q3W, pemetrexed 500 mg/m2 , and carboplatin AUC5 or cisplatin 75 mg/m2 were randomized 1:1 to olaparib 300 mg orally twice daily or pemetrexed Q3W, both given with ≤31 cycles of pembrolizumab Q3W. Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). PFS was tested at interim analysis 2 (IA2; ie, final PFS analysis), OS at final analysis (FA).
Results: Of 1003 patients who received induction therapy, 672 (67.0%) were randomized to pembrolizumab plus olaparib (n=337) or pembrolizumab plus pemetrexed (n=335) in the intention-to-treat population. Median follow-up at FA was 39.9 (range, 28.1-51.5) months. At IA2, median (95% CI) PFS was 7.1 (5.6-8.7) months versus 8.3 (6.9-11.5) months in the olaparib versus pemetrexed groups (HR, 1.12; 95% CI, 0.92-1.36; P=0.87). At FA, median (95% CI) OS was 20.7 (18.0-24.8) months versus 23.0 (19.0-26.4) months (HR, 1.04; 95% CI, 0.87-1.25; P=0.6649). Grade 3-5 maintenance treatment-related AEs occurred in 26.1% versus 30.1% patients.
Conclusion: Pembrolizumab plus maintenance olaparib did not improve PFS or OS versus pembrolizumab plus pemetrexed in previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations.
期刊介绍：
Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer,is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies.The readship includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology.
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