Michael Offin1, Narek Shaverdian2, Andreas Rimner3, Stephanie Lobaugh4, Annemarie F Shepherd5, Charles B Simone6, Daphna Y Gelblum7, Abraham J Wu8, Nancy Lee9, Mark G Kris10, Charles M Rudin11, Zhigang Zhang12, Matthew D Hellmann13, Jamie E Chaft14, Daniel R Gomez15. 1. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, United States. Electronic address: offinm@mskcc.org. 2. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Electronic address: shaverdn@mskcc.org. 3. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Electronic address: rimnera@mskcc.org. 4. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Electronic address: lobaughs@mskcc.org. 5. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Electronic address: shephera@mskcc.org. 6. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Electronic address: simonec1@mskcc.org. 7. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Electronic address: gelblumd@mskcc.org. 8. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Electronic address: wua@mskcc.org. 9. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Electronic address: leen2@mskcc.org. 10. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, United States. Electronic address: krism@mskcc.org. 11. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, United States. Electronic address: rudinc@mskcc.org. 12. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Electronic address: zhangz@mskcc.org. 13. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, United States. Electronic address: hellmanm@mskcc.org. 14. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, United States. Electronic address: chaftj@mskcc.org. 15. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, United States. Electronic address: gomezd@mskcc.org.
Abstract
BACKGROUND AND PURPOSE: Concurrent chemoradiation (cCRT) and durvalumab is standard therapy for patients with unresectable stage III non-small-cell lung cancers (NSCLC). Data is limited on outcomes with this regimen outside of clinical trials. Local-regional control rates remain undefined. MATERIALS AND METHODS: We reviewed patients with stage III unresectable NSCLCs treated between November 2017 and February 2019 with cCRT and ≥1 dose of durvalumab. We examined 12-month progression-free-survival (PFS), overall-survival (OS), toxicities, and the incidence and pattern of local-regional and metastatic failures. RESULTS: Sixty-two patients (median follow-up 12 months) with median age of 66 years of which 73% had stage IIIB (n = 33) or IIIC (n = 12) disease started durvalumab a median of 1.5 months from the end of cCRT and were treated with a median of 8 months of durvalumab. Common reasons for stopping durvalumab included disease progression (32%, 20/62) and toxicity (24%, 15/62). The estimated 12-month PFS and OS were 65% (95% CI: 51-79%) and 85% (95% CI: 75-95%), respectively. The cumulative 12-month incidence of local-regional and distant failures were 18% (95% CI: 5.9-30%) and 30% (95% CI: 16.3-44.5%), respectively. Among patients with distant metastatic disease (n = 17), 47% had oligometastatic disease. High tumor mutation burden (≥8.8 mt/Mb) or PD-L1 (≥1% or PD-L1 ≥ 50%) did not predict improved PFS. CONCLUSIONS: Outcomes with cCRT and durvalumab in practice align with the PACIFIC trial. A substantial minority of patients are candidates for metastasis-directed therapies at progression. Local regional outcomes appear improved to historical data of cCRT alone.
BACKGROUND AND PURPOSE: Concurrent chemoradiation (cCRT) and durvalumab is standard therapy for patients with unresectable stage III non-small-cell lung cancers (NSCLC). Data is limited on outcomes with this regimen outside of clinical trials. Local-regional control rates remain undefined. MATERIALS AND METHODS: We reviewed patients with stage III unresectable NSCLCs treated between November 2017 and February 2019 with cCRT and ≥1 dose of durvalumab. We examined 12-month progression-free-survival (PFS), overall-survival (OS), toxicities, and the incidence and pattern of local-regional and metastatic failures. RESULTS: Sixty-two patients (median follow-up 12 months) with median age of 66 years of which 73% had stage IIIB (n = 33) or IIIC (n = 12) disease started durvalumab a median of 1.5 months from the end of cCRT and were treated with a median of 8 months of durvalumab. Common reasons for stopping durvalumab included disease progression (32%, 20/62) and toxicity (24%, 15/62). The estimated 12-month PFS and OS were 65% (95% CI: 51-79%) and 85% (95% CI: 75-95%), respectively. The cumulative 12-month incidence of local-regional and distant failures were 18% (95% CI: 5.9-30%) and 30% (95% CI: 16.3-44.5%), respectively. Among patients with distant metastatic disease (n = 17), 47% had oligometastatic disease. High tumor mutation burden (≥8.8 mt/Mb) or PD-L1 (≥1% or PD-L1 ≥ 50%) did not predict improved PFS. CONCLUSIONS: Outcomes with cCRT and durvalumab in practice align with the PACIFIC trial. A substantial minority of patients are candidates for metastasis-directed therapies at progression. Local regional outcomes appear improved to historical data of cCRT alone.
Authors: Narek Shaverdian; Michael Offin; Annemarie F Shepherd; Charles B Simone; Daphna Y Gelblum; Abraham J Wu; Matthew D Hellmann; Andreas Rimner; Paul K Paik; Jamie E Chaft; Daniel R Gomez Journal: J Thorac Oncol Date: 2021-05-13 Impact factor: 20.121
Authors: Maria Thor; Annemarie F Shepherd; Isabel Preeshagul; Michael Offin; Daphna Y Gelblum; Abraham J Wu; Aditya Apte; Charles B Simone; Matthew D Hellmann; Andreas Rimner; Jamie E Chaft; Daniel R Gomez; Joseph O Deasy; Narek Shaverdian Journal: Radiother Oncol Date: 2021-12-20 Impact factor: 6.901
Authors: Narek Shaverdian; Michael Offin; Annemarie F Shepherd; Matthew D Hellmann; Daniel R Gomez; Jamie E Chaft; Andreas Rimner Journal: JTO Clin Res Rep Date: 2021-06-10