Greg A Durm1, Salma K Jabbour2, Sandra K Althouse3, Ziyue Liu3, Ahad A Sadiq4, Robin T Zon5, Shadia I Jalal1,6, Goetz H Kloecker7, Michael J Williamson8, Karen L Reckamp9, Robert M Langdon10, Ebenezer A Kio11, Ryan D Gentzler12, Bamidele A Adesunloye13, Wael A Harb14, Radhika V Walling15, Michael L Titzer16, Nasser H Hanna1. 1. Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana. 2. Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. 3. Department of Biostatistics, Indiana University, Indianapolis, Indiana. 4. Fort Wayne Medical Oncology and Hematology, Fort Wayne, Indiana. 5. Michiana Hematology Oncology, South Bend, Indiana. 6. Richard L. Roudebush VA Medical Center, Indianapolis, Indiana. 7. James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky. 8. Indiana University Health Ball Memorial Cancer Center, Muncie, Indiana. 9. City of Hope Comprehensive Cancer Center, Duarte, California. 10. Nebraska Methodist Hospital, Omaha, Nebraska. 11. Goshen Center for Cancer Care, Goshen, Indiana. 12. University of Virginia, Charlottesville, Virginia. 13. Indiana University Health Arnett Cancer Center, Lafayette, Indiana. 14. Horizon Oncology Center, Lafayette, Indiana. 15. Community Regional Cancer Center, Indianapolis, Indiana. 16. Oncology Hematology Associates of Southwest Indiana, Newburgh, Indiana.
Abstract
BACKGROUND: Five-year overall survival (OS) for patients with unresectable stage III non-small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti-programmed death 1 antibodies have demonstrated improved OS. This trial evaluated pembrolizumab as consolidation therapy after concurrent chemoradiation in patients with unresectable stage III disease. METHODS: Patients with unresectable stage III NSCLC received concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel and 59.4 to 66.6 Gy of radiation. Patients with nonprogression of disease were enrolled and received pembrolizumab (200 mg intravenously every 3 weeks for up to 12 months). The primary endpoint was the time to metastatic disease or death (TMDD). Secondary endpoints included progression-free survival (PFS) and OS. RESULTS: The median follow-up for 93 patients (92 for efficacy) was 32.2 months (range, 1.2-46.6 months). The median TMDD was 30.7 months (95% confidence interval [CI], 18.7 months to not reached), which was significantly longer than the historical control of 12 months (P < .0001). The median PFS was 18.7 months (95% CI, 12.4-33.8 months), and the median OS was 35.8 months (95% CI, 24.2 months to not reached). The 1-, 2-, and 3-year OS estimates were 81.2%, 62.0%, and 48.5%, respectively. Forty patients (43.5%) completed 12 months of treatment (median number of cycles, 13.5). Symptomatic pneumonitis (grade 2 or higher) was noted in 16 patients (17.2%); these cases included 4 grade 3 events (4.3%), 1 grade 4 event (1.1%), and 1 grade 5 event (1.1%). CONCLUSIONS: Consolidation pembrolizumab after concurrent chemoradiation improves TMDD, PFS, and OS in comparison with historical controls of chemoradiation alone. Rates of grade 3 to 5 pneumonitis were similar to those reported with chemoradiation alone.
BACKGROUND: Five-year overall survival (OS) for patients with unresectable stage III non-small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti-programmed death 1 antibodies have demonstrated improved OS. This trial evaluated pembrolizumab as consolidation therapy after concurrent chemoradiation in patients with unresectable stage III disease. METHODS:Patients with unresectable stage III NSCLC received concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel and 59.4 to 66.6 Gy of radiation. Patients with nonprogression of disease were enrolled and received pembrolizumab (200 mg intravenously every 3 weeks for up to 12 months). The primary endpoint was the time to metastatic disease or death (TMDD). Secondary endpoints included progression-free survival (PFS) and OS. RESULTS: The median follow-up for 93 patients (92 for efficacy) was 32.2 months (range, 1.2-46.6 months). The median TMDD was 30.7 months (95% confidence interval [CI], 18.7 months to not reached), which was significantly longer than the historical control of 12 months (P < .0001). The median PFS was 18.7 months (95% CI, 12.4-33.8 months), and the median OS was 35.8 months (95% CI, 24.2 months to not reached). The 1-, 2-, and 3-year OS estimates were 81.2%, 62.0%, and 48.5%, respectively. Forty patients (43.5%) completed 12 months of treatment (median number of cycles, 13.5). Symptomatic pneumonitis (grade 2 or higher) was noted in 16 patients (17.2%); these cases included 4 grade 3 events (4.3%), 1 grade 4 event (1.1%), and 1 grade 5 event (1.1%). CONCLUSIONS: Consolidation pembrolizumab after concurrent chemoradiation improves TMDD, PFS, and OS in comparison with historical controls of chemoradiation alone. Rates of grade 3 to 5 pneumonitis were similar to those reported with chemoradiation alone.
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Authors: John M Varlotto; Zhuoxin Sun; Bonnie Ky; Jenica Upshaw; Sharyn I Katz; Thomas J Fitzgerald; Heather Wakelee; Maximilian Diehn; David A Mankoff; Christine Lovely; Chandra Belani; Kurt Oettel; Gregory Masters; Suresh Ramalingam; Nathan A Pennell Journal: Oncologist Date: 2021-03-11
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