Pembrolizumab and Pemetrexed for Older Patients With Nonsquamous NSCLC and Programmed Cell Death-Ligand 1 Tumor Proportion Scores of Less Than 50%
Introduction: Pembrolizumab with pemetrexed and cisplatin/carboplatin is an approved first-line treatment for metastatic nonsquamous NSCLC. Nevertheless, its efficacy and safety in patients aged 75 years and above remain unclear. We assessed the efficacy and safety of pembrolizumab with pemetrexed i...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
|
| Series: | JTO Clinical and Research Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364324001541 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823864238992523264 |
|---|---|
| author | Yoshihito Kogure, MD, PhD Hiroya Hashimoto, PhD Haruko Daga, MD, PhD Yasushi Fukuda, MD Akihiro Bessho, MD, PhD Tadaaki Yamada, MD, PhD Yukihiro Toi, MD Tomoki Kimura, MD, PhD Hiroshige Yoshioka, MD, PhD Koichi Azuma, MD, PhD Naoki Furuya, MD, PhD Yasutaka Fukui, MD, PhD Akiko M. Saito, MD, PhD Nobuyuki Yamamoto, MD, PhD Hideo Saka, MD Masashi Kondo, MD, PhD |
| author_facet | Yoshihito Kogure, MD, PhD Hiroya Hashimoto, PhD Haruko Daga, MD, PhD Yasushi Fukuda, MD Akihiro Bessho, MD, PhD Tadaaki Yamada, MD, PhD Yukihiro Toi, MD Tomoki Kimura, MD, PhD Hiroshige Yoshioka, MD, PhD Koichi Azuma, MD, PhD Naoki Furuya, MD, PhD Yasutaka Fukui, MD, PhD Akiko M. Saito, MD, PhD Nobuyuki Yamamoto, MD, PhD Hideo Saka, MD Masashi Kondo, MD, PhD |
| author_sort | Yoshihito Kogure, MD, PhD |
| collection | DOAJ |
| description | Introduction: Pembrolizumab with pemetrexed and cisplatin/carboplatin is an approved first-line treatment for metastatic nonsquamous NSCLC. Nevertheless, its efficacy and safety in patients aged 75 years and above remain unclear. We assessed the efficacy and safety of pembrolizumab with pemetrexed in patients with programmed cell death-ligand 1 expression tumor proportion scores of less than 50%. Methods: This multicenter, open-label, phase 2 trial involved 42 institutions across Japan. Eligible participants had metastatic or recurrent nonsquamous NSCLC without sensitizing EGFR or ALK alterations, were aged 75 years or above, had a programmed cell death-ligand 1 tumor proportion score of less than 50%, had not undergone systemic chemotherapy, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pemetrexed (500 mg/m2) and pembrolizumab (200 mg) on day 1 of each 21-day cycle. The primary endpoint was the objective response rate. The secondary endpoints included progression-free survival, overall survival, and safety. Results: Forty-nine patients were enrolled in this study between July 2020 and May 2022. The objective response rate was 36.7% (95% confidence interval [CI]: 23.4%–51.7%). The disease control rate was 65.3% (95% CI: 50.4–78.3%). The median progression-free survival was 7.6 months (95% CI: 4.8–16.2), and the median overall survival was 19.4 months (95% CI: 11.8 mo–unreached). The most common grade 3 or 4 adverse events were neutropenia (31.3%), leukopenia (20.8%), and anemia (12.5%). No treatment-related deaths occurred during this period. Conclusions: Pembrolizumab with pemetrexed is a promising first-line treatment option for older patients with metastatic nonsquamous NSCLC. This trial was registered at ClinicalTrials.gov (NCT04396457) and the Japan Registry of Clinical Trials (jRCTs041200012). |
| format | Article |
| id | doaj-art-580deb053391415d8c58b6244067754c |
| institution | Kabale University |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj-art-580deb053391415d8c58b6244067754c2025-02-09T05:01:29ZengElsevierJTO Clinical and Research Reports2666-36432025-03-0163100784Pembrolizumab and Pemetrexed for Older Patients With Nonsquamous NSCLC and Programmed Cell Death-Ligand 1 Tumor Proportion Scores of Less Than 50%Yoshihito Kogure, MD, PhD0Hiroya Hashimoto, PhD1Haruko Daga, MD, PhD2Yasushi Fukuda, MD3Akihiro Bessho, MD, PhD4Tadaaki Yamada, MD, PhD5Yukihiro Toi, MD6Tomoki Kimura, MD, PhD7Hiroshige Yoshioka, MD, PhD8Koichi Azuma, MD, PhD9Naoki Furuya, MD, PhD10Yasutaka Fukui, MD, PhD11Akiko M. Saito, MD, PhD12Nobuyuki Yamamoto, MD, PhD13Hideo Saka, MD14Masashi Kondo, MD, PhD15Department of Respiratory Medicine, NHO Nagoya Medical Center, Nagoya, Japan; Corresponding author. Address for correspondence: Yoshihito Kogure, MD, PhD, Department of Respiratory Medicine, NHO Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya 460-0001, Japan.Clinical Research Center, NHO Nagoya Medical Center, Nagoya, JapanDepartment of Medical Oncology, Osaka City General Hospital, Osaka, JapanDepartment of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, JapanDepartment of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, JapanDepartment of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Kyoto, JapanDepartment of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, JapanDepartment of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, JapanDepartment of Thoracic Oncology, Kansai Medical University, Hirakata, JapanDepartment of Internal Medicine, Division of Respirology, Neurology, and Rheumatology, Kurume University School of Medicine, Kurume-Shi, JapanDivision of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, JapanDepartment of Respiratory Medicine, Toyohashi Municipal Hospital, Toyohashi, JapanClinical Research Center, NHO Nagoya Medical Center, Nagoya, JapanDepartment of Pulmonary Medicine and Medical Oncology, Wakayama Medical University, Wakayama, JapanDepartment of Respiratory Medicine, NHO Nagoya Medical Center, Nagoya, Japan; Department of Respiratory Medicine, Matsunami General Hospital, Kasamatsu, JapanDepartment of Respiratory Medicine, Fujita Health University School of Medicine, Toyoake, JapanIntroduction: Pembrolizumab with pemetrexed and cisplatin/carboplatin is an approved first-line treatment for metastatic nonsquamous NSCLC. Nevertheless, its efficacy and safety in patients aged 75 years and above remain unclear. We assessed the efficacy and safety of pembrolizumab with pemetrexed in patients with programmed cell death-ligand 1 expression tumor proportion scores of less than 50%. Methods: This multicenter, open-label, phase 2 trial involved 42 institutions across Japan. Eligible participants had metastatic or recurrent nonsquamous NSCLC without sensitizing EGFR or ALK alterations, were aged 75 years or above, had a programmed cell death-ligand 1 tumor proportion score of less than 50%, had not undergone systemic chemotherapy, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pemetrexed (500 mg/m2) and pembrolizumab (200 mg) on day 1 of each 21-day cycle. The primary endpoint was the objective response rate. The secondary endpoints included progression-free survival, overall survival, and safety. Results: Forty-nine patients were enrolled in this study between July 2020 and May 2022. The objective response rate was 36.7% (95% confidence interval [CI]: 23.4%–51.7%). The disease control rate was 65.3% (95% CI: 50.4–78.3%). The median progression-free survival was 7.6 months (95% CI: 4.8–16.2), and the median overall survival was 19.4 months (95% CI: 11.8 mo–unreached). The most common grade 3 or 4 adverse events were neutropenia (31.3%), leukopenia (20.8%), and anemia (12.5%). No treatment-related deaths occurred during this period. Conclusions: Pembrolizumab with pemetrexed is a promising first-line treatment option for older patients with metastatic nonsquamous NSCLC. This trial was registered at ClinicalTrials.gov (NCT04396457) and the Japan Registry of Clinical Trials (jRCTs041200012).http://www.sciencedirect.com/science/article/pii/S2666364324001541PembrolizumabPemetrexedNonsquamous non-small cell lung cancerOlder patientsProgrammed cell death 1 |
| spellingShingle | Yoshihito Kogure, MD, PhD Hiroya Hashimoto, PhD Haruko Daga, MD, PhD Yasushi Fukuda, MD Akihiro Bessho, MD, PhD Tadaaki Yamada, MD, PhD Yukihiro Toi, MD Tomoki Kimura, MD, PhD Hiroshige Yoshioka, MD, PhD Koichi Azuma, MD, PhD Naoki Furuya, MD, PhD Yasutaka Fukui, MD, PhD Akiko M. Saito, MD, PhD Nobuyuki Yamamoto, MD, PhD Hideo Saka, MD Masashi Kondo, MD, PhD Pembrolizumab and Pemetrexed for Older Patients With Nonsquamous NSCLC and Programmed Cell Death-Ligand 1 Tumor Proportion Scores of Less Than 50% JTO Clinical and Research Reports Pembrolizumab Pemetrexed Nonsquamous non-small cell lung cancer Older patients Programmed cell death 1 |
| title | Pembrolizumab and Pemetrexed for Older Patients With Nonsquamous NSCLC and Programmed Cell Death-Ligand 1 Tumor Proportion Scores of Less Than 50% |
| title_full | Pembrolizumab and Pemetrexed for Older Patients With Nonsquamous NSCLC and Programmed Cell Death-Ligand 1 Tumor Proportion Scores of Less Than 50% |
| title_fullStr | Pembrolizumab and Pemetrexed for Older Patients With Nonsquamous NSCLC and Programmed Cell Death-Ligand 1 Tumor Proportion Scores of Less Than 50% |
| title_full_unstemmed | Pembrolizumab and Pemetrexed for Older Patients With Nonsquamous NSCLC and Programmed Cell Death-Ligand 1 Tumor Proportion Scores of Less Than 50% |
| title_short | Pembrolizumab and Pemetrexed for Older Patients With Nonsquamous NSCLC and Programmed Cell Death-Ligand 1 Tumor Proportion Scores of Less Than 50% |
| title_sort | pembrolizumab and pemetrexed for older patients with nonsquamous nsclc and programmed cell death ligand 1 tumor proportion scores of less than 50 |
| topic | Pembrolizumab Pemetrexed Nonsquamous non-small cell lung cancer Older patients Programmed cell death 1 |
| url | http://www.sciencedirect.com/science/article/pii/S2666364324001541 |
| work_keys_str_mv | AT yoshihitokoguremdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT hiroyahashimotophd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT harukodagamdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT yasushifukudamd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT akihirobesshomdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT tadaakiyamadamdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT yukihirotoimd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT tomokikimuramdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT hiroshigeyoshiokamdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT koichiazumamdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT naokifuruyamdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT yasutakafukuimdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT akikomsaitomdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT nobuyukiyamamotomdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT hideosakamd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 AT masashikondomdphd pembrolizumabandpemetrexedforolderpatientswithnonsquamousnsclcandprogrammedcelldeathligand1tumorproportionscoresoflessthan50 |