Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial
Background In this phase I/II trial, we evaluated the safety and effectiveness of pembrolizumab, with or without concurrent radiotherapy (RT), for lung and liver lesions from metastatic non-small cell lung cancer (mNSCLC).Methods Patients with lung or liver lesions amenable to RT plus at least one a...
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BMJ Publishing Group
2020-07-01
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Series: | Journal for ImmunoTherapy of Cancer |
Online Access: | https://jitc.bmj.com/content/8/2/e001001.full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hari Menon Dawei Chen Vivek Verma Mehmet Altan John V Heymach Quynh-Nhu Nguyen Rejani Varghese Nathan I Comeaux George Simon Ferdinandos Skoulidis Joe Y Chang Vasiliki Papdimitrakopoulou Steven H Lin |
spellingShingle |
Hari Menon Dawei Chen Vivek Verma Mehmet Altan John V Heymach Quynh-Nhu Nguyen Rejani Varghese Nathan I Comeaux George Simon Ferdinandos Skoulidis Joe Y Chang Vasiliki Papdimitrakopoulou Steven H Lin Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial Journal for ImmunoTherapy of Cancer |
author_facet |
Hari Menon Dawei Chen Vivek Verma Mehmet Altan John V Heymach Quynh-Nhu Nguyen Rejani Varghese Nathan I Comeaux George Simon Ferdinandos Skoulidis Joe Y Chang Vasiliki Papdimitrakopoulou Steven H Lin |
author_sort |
Hari Menon |
title |
Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial |
title_short |
Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial |
title_full |
Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial |
title_fullStr |
Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial |
title_full_unstemmed |
Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial |
title_sort |
pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase i/ii trial |
publisher |
BMJ Publishing Group |
series |
Journal for ImmunoTherapy of Cancer |
issn |
2051-1426 |
publishDate |
2020-07-01 |
description |
Background In this phase I/II trial, we evaluated the safety and effectiveness of pembrolizumab, with or without concurrent radiotherapy (RT), for lung and liver lesions from metastatic non-small cell lung cancer (mNSCLC).Methods Patients with lung or liver lesions amenable to RT plus at least one additional non-contiguous lesion were included regardless of programmed death-ligand 1 (PD-L1) status. Pembrolizumab was given at 200 mg every 3 weeks for up to 32 cycles with or without concurrent RT. Metastatic lesions were treated with stereotactic body RT (SBRT; 50 Gy in 4 fractions) if clinically feasible or with traditionally fractionated RT (45 Gy in 15 fractions) if not. The primary end point was the best out-of-field lesion response, and a key secondary end point was progression-free survival (PFS).Results The median follow-up time was 20.4 months. One hundred patients (20 phase I, 80 phase II) were evaluable for toxicity, and 72 phase II patients were evaluable for treatment response. No patients in the phase I group experienced grade 4–5 events; in the phase II group, two had grade 4 events and nine had grade 3 events. The ORR in the combined-modality cohort (irrespective of RT schema) was 22%, vs 25% in the pembrolizumab group (irrespective of receipt of salvage RT) (p=0.99). In the concurrent pembrolizumab+RT groups, the out-of-field ORRs were 38% in the pembrolizumab+SBRT group and 10% in the pembrolizumab+traditional RT group. When examining the pembrolizumab-alone patients, the out-of-field ORRs were 33% in those designated to receive salvage SBRT (if required) and 17% for salvage traditional RT. In all patients, the median PFS for pembrolizumab alone was 5.1 months (95% CI 3.4 to 12.7 months), and pembrolizumab/RT (regardless of schema) was 9.1 months (95% CI 3.6 to 18.4 months) (p=0.52). An exploratory analysis revealed that for patients with low PD-L1 expression, the median PFS was 4.6 vs 20.8 months for pembrolizumab with and without RT, respectively (p=0.004).Conclusions Concurrent immunoradiotherapy for mNSCLC is safe, although larger trials are required to address which patients benefit most from RT.Trial registration number NCT02444741. |
url |
https://jitc.bmj.com/content/8/2/e001001.full |
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doaj-b400a5d6542a4cae80f1c87d5bc305832021-07-13T15:01:38ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-07-018210.1136/jitc-2020-001001Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trialHari Menon0Dawei Chen1Vivek Verma2Mehmet Altan3John V Heymach4Quynh-Nhu Nguyen5Rejani Varghese6Nathan I Comeaux7George Simon8Ferdinandos Skoulidis9Joe Y Chang10Vasiliki Papdimitrakopoulou11Steven H Lin12Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States1 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China 6 Department of Radiation oncology, Allegheny General Hospital, Pittsburgh, United States Aff9 0000 0001 2291 4776grid.240145.6Thoracic Head and Neck Medical OncologyThe University of Texas MD Anderson Cancer Center 1515 Holcombe Blvd Houston TX USA Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USARadiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United StatesRadiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United StatesRadiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United StatesRadiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United StatesThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USARadiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United StatesRadiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United StatesRadiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United StatesBackground In this phase I/II trial, we evaluated the safety and effectiveness of pembrolizumab, with or without concurrent radiotherapy (RT), for lung and liver lesions from metastatic non-small cell lung cancer (mNSCLC).Methods Patients with lung or liver lesions amenable to RT plus at least one additional non-contiguous lesion were included regardless of programmed death-ligand 1 (PD-L1) status. Pembrolizumab was given at 200 mg every 3 weeks for up to 32 cycles with or without concurrent RT. Metastatic lesions were treated with stereotactic body RT (SBRT; 50 Gy in 4 fractions) if clinically feasible or with traditionally fractionated RT (45 Gy in 15 fractions) if not. The primary end point was the best out-of-field lesion response, and a key secondary end point was progression-free survival (PFS).Results The median follow-up time was 20.4 months. One hundred patients (20 phase I, 80 phase II) were evaluable for toxicity, and 72 phase II patients were evaluable for treatment response. No patients in the phase I group experienced grade 4–5 events; in the phase II group, two had grade 4 events and nine had grade 3 events. The ORR in the combined-modality cohort (irrespective of RT schema) was 22%, vs 25% in the pembrolizumab group (irrespective of receipt of salvage RT) (p=0.99). In the concurrent pembrolizumab+RT groups, the out-of-field ORRs were 38% in the pembrolizumab+SBRT group and 10% in the pembrolizumab+traditional RT group. When examining the pembrolizumab-alone patients, the out-of-field ORRs were 33% in those designated to receive salvage SBRT (if required) and 17% for salvage traditional RT. In all patients, the median PFS for pembrolizumab alone was 5.1 months (95% CI 3.4 to 12.7 months), and pembrolizumab/RT (regardless of schema) was 9.1 months (95% CI 3.6 to 18.4 months) (p=0.52). An exploratory analysis revealed that for patients with low PD-L1 expression, the median PFS was 4.6 vs 20.8 months for pembrolizumab with and without RT, respectively (p=0.004).Conclusions Concurrent immunoradiotherapy for mNSCLC is safe, although larger trials are required to address which patients benefit most from RT.Trial registration number NCT02444741.https://jitc.bmj.com/content/8/2/e001001.full |