James W Welsh1, John V Heymach2, Dawei Chen3, Vivek Verma4, Taylor R Cushman5, Kenneth R Hess6, Girish Shroff7, Chad Tang5, Ferdinandos Skoulidis2, Melenda Jeter5, Hari Menon5, Quynh-Nhu Nguyen5, Joe Y Chang5, Mehmet Altan2, Vassiliki A Papadimitrakopoulou2, George R Simon2, Uma Raju5, Lauren Byers2, Bonnie Glisson2. 1. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: jwelsh@mdanderson.org. 2. Department of Thoracic Head & Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 3. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, China. 4. Department of Radiation Oncology, Alleghany General Hospital, Pittsburgh, Pennsylvania. 5. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 6. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 7. Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Abstract
INTRUDUCTION: Radiation and immunotherapy have separately been shown to confer survival advantages to patients with extensive-stage small cell lung cancer (ESCLC), but failure rates remain high and combination therapy has been understudied. In this single-arm phase I trial (NCT02402920), we assessed the safety of combining pembrolizumab with thoracic radiotherapy (TRT) after induction chemotherapy for SCLC. METHODS: Patients with ESCLC who had completed chemotherapy received TRT with pembrolizumab. The maximum tolerated dose of pembrolizumab was assessed by 3+3 dose-escalation; doses began at 100 mg and increased in 50 mg increments to 200 mg. Pembrolizumab was given every 3 weeks for up to 16 cycles; TRT was prescribed as 45 Gy in 15 daily fractions. Toxicity was evaluated with the Common Terminology Criteria for Adverse Events v4.0. The primary endpoint was safety of the combined therapy based on the incidence of dose-limiting toxicity in the 35 days following initiation of treatment. RESULTS: Thirty-eight patients with ESCLC (median age 65 years, range: 37-79 years) were enrolled from September 2015 through September 2017; 33 received per-protocol treatment, and all tolerated pembrolizumab at 100 to 200 mg with no dose-limiting toxicity in the 35-day window. There were no grade 4-5 toxicities; 2 (6%) patients experienced grade 3 events (n = 1 rash, n = 1 asthenia/paresthesia/autoimmune disorder) that were unlikely/doubtfully related to protocol therapy. The median follow-up time was 7.3 months (range: 1-13 months); median progression-free and overall survival times were 6.1 months (95% confidence interval: 4.1-8.1) and 8.4 months (95% confidence interval: 6.7-10.1). CONCLUSIONS: Concurrent pembrolizumab-TRT was tolerated well with few high-grade adverse events in the short-term; progression-free and overall survival rates are difficult to interpret due to heterogeneity in eligibility criteria (e.g., enrolling progressors on induction chemotherapy). Although randomized studies have shown benefits to TRT alone and immunotherapy alone, the safety of the combined regimen supports further investigation as a foundational approach for future prospective studies.
INTRUDUCTION: Radiation and immunotherapy have separately been shown to confer survival advantages to patients with extensive-stage small cell lung cancer (ESCLC), but failure rates remain high and combination therapy has been understudied. In this single-arm phase I trial (NCT02402920), we assessed the safety of combining pembrolizumab with thoracic radiotherapy (TRT) after induction chemotherapy for SCLC. METHODS:Patients with ESCLC who had completed chemotherapy received TRT with pembrolizumab. The maximum tolerated dose of pembrolizumab was assessed by 3+3 dose-escalation; doses began at 100 mg and increased in 50 mg increments to 200 mg. Pembrolizumab was given every 3 weeks for up to 16 cycles; TRT was prescribed as 45 Gy in 15 daily fractions. Toxicity was evaluated with the Common Terminology Criteria for Adverse Events v4.0. The primary endpoint was safety of the combined therapy based on the incidence of dose-limiting toxicity in the 35 days following initiation of treatment. RESULTS: Thirty-eight patients with ESCLC (median age 65 years, range: 37-79 years) were enrolled from September 2015 through September 2017; 33 received per-protocol treatment, and all tolerated pembrolizumab at 100 to 200 mg with no dose-limiting toxicity in the 35-day window. There were no grade 4-5 toxicities; 2 (6%) patients experienced grade 3 events (n = 1 rash, n = 1 asthenia/paresthesia/autoimmune disorder) that were unlikely/doubtfully related to protocol therapy. The median follow-up time was 7.3 months (range: 1-13 months); median progression-free and overall survival times were 6.1 months (95% confidence interval: 4.1-8.1) and 8.4 months (95% confidence interval: 6.7-10.1). CONCLUSIONS: Concurrent pembrolizumab-TRT was tolerated well with few high-grade adverse events in the short-term; progression-free and overall survival rates are difficult to interpret due to heterogeneity in eligibility criteria (e.g., enrolling progressors on induction chemotherapy). Although randomized studies have shown benefits to TRT alone and immunotherapy alone, the safety of the combined regimen supports further investigation as a foundational approach for future prospective studies.
Authors: Daphne W Dumoulin; Anne-Marie C Dingemans; Joachim G J V Aerts; Jordi Remon; Dirk K M De Ruysscher; Lizza E L Hendriks Journal: Transl Lung Cancer Res Date: 2021-06
Authors: Bradford A Perez; Sungjune Kim; Minhsuan Wang; Ahmad M Karimi; Chase Powell; Jiannong Li; Thomas J Dilling; Alberto Chiappori; Kujtim Latifi; Trevor Rose; Austin Lannon; Gretchen MacMillan; James Saller; G Daniel Grass; Stephen Rosenberg; Jhanelle Gray; Eric Haura; Ben Creelan; Tawee Tanvetyanon; Andreas Saltos; Michael Shafique; Theresa A Boyle; Michael J Schell; Jose R Conejo-Garcia; Scott J Antonia Journal: Int J Radiat Oncol Biol Phys Date: 2020-09-28 Impact factor: 7.038