Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial
Authors: Kenneth Hess
John V Heymach
Mehmet Altan
Nathan I Comeaux
Chad Tang
Vivek Verma
Rejani Varghese
Steven H Lin
James Welsh
Quynh-Nhu Nguyen
Patricia de Groot
Joe Y Chang
George Simon
Vasiliki Papdimitrakopoulou
Ferdinandos Skoulidis
Dawei Chen
Hari Menon
Journal: Journal for ImmunoTherapy of Cancer (2020)
Discipline: IMMUNOLOGY
Keywords: immunotherapy; lung neoplasms; radioimmunotherapy; radiotherapy.
Affiliations: Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States ., Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States., Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China., Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania., Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Biostatistics, MD Anderson Cancer Center, Houston, United States., Division of Diagnostic Imaging, Department of Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, United States.

Abstract:  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. 

Retracted: No

PubPeer comments:
 In figure3F, the risk table dose not match the survival curve. ![file] Totally 10 patients in pembrolizumab group and all of them are marked in survival curve (red line). At 15 months, 7 patients had reached the end-point or censored, thus remaining 3 patients at risk. At 20 months, just same as 15 months, there are also 7 patients out of following and the rest 3 patients at risk. According to the survival curve, these 3 patients who are followed more than 20 months censored in the time of 21.5 months, 24.8 months and 27.2 months. But in the risk table in lower panel, at 20 months, only 1 patient pembrolizumab group is at risk. Hope the authors check their survival data. ,