Jacqueline V Aredo1, Isa Mambetsariev2, Jessica A Hellyer3, Arya Amini4, Joel W Neal3, Sukhmani K Padda3, Caroline E McCoach5, Jonathan W Riess6, Elwyn C Cabebe7, Jarushka Naidoo8, Tariq Abuali4, Ravi Salgia2, Billy W Loo9, Maximilian Diehn9, Summer S Han10, Heather A Wakelee11. 1. Stanford University School of Medicine, Stanford, California. 2. Department of Medical Oncology & Therapeutics Research, City of Hope Medical Center, Duarte, California. 3. Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California. 4. Department of Radiation Oncology, City of Hope Medical Center, Duarte, California. 5. UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. 6. Division of Hematology and Oncology, Department of Internal Medicine, UC Davis Comprehensive Cancer Center, Sacramento, California. 7. Stanford Health Care, University Healthcare Alliance, Stanford Cancer Center South Bay, San Jose, California. 8. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland; Department of Oncology, Beaumont Hospital Dublin, The Royal College of Surgeons of Ireland, Dublin, Ireland. 9. Department of Radiation Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California. 10. Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, California. 11. Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California. Electronic address: hwakelee@stanford.edu.
Abstract
INTRODUCTION: In 2018, durvalumab was approved by the U.S. Food and Drug Administration as consolidation immunotherapy for patients with stage III NSCLC after definitive chemoradiotherapy (CRT). However, whether durvalumab benefits patients with EGFR-mutated NSCLC remains unknown. METHODS: We conducted a multi-institutional retrospective analysis of patients with unresectable stage III EGFR-mutated NSCLC who completed concurrent CRT. Kaplan-Meier analyses evaluated progression-free survival (PFS) between patients who completed CRT with or without durvalumab. RESULTS: Among 37 patients, 13 initiated durvalumab a median of 20 days after CRT completion. Two patients completed 12 months of treatment, with five patients discontinuing durvalumab owing to progression and five owing to immune-related adverse events (irAEs). Of 24 patients who completed CRT without durvalumab, 16 completed CRT alone and eight completed CRT with induction or consolidation EGFR tyrosine kinase inhibitors (TKIs). Median PFS was 10.3 months in patients who received CRT and durvalumab versus 6.9 months with CRT alone (log-rank p = 0.993). CRT and EGFR TKI was associated with a significantly longer median PFS (26.1 mo) compared with CRT and durvalumab or CRT alone (log-rank p = 0.023). Six patients treated with durvalumab initiated EGFR TKIs after recurrence, with one developing grade 4 pneumonitis on osimertinib. CONCLUSIONS: In this study, patients with EGFR-mutated NSCLC did not benefit with consolidation durvalumab and experienced a high frequency of irAEs. Patients who initiate osimertinib after durvalumab may be susceptible to incident irAEs. Consolidation durvalumab should be approached with caution in this setting and concurrent CRT with induction or consolidation EGFR TKIs further investigated as definitive treatment.
INTRODUCTION: In 2018, durvalumab was approved by the U.S. Food and Drug Administration as consolidation immunotherapy for patients with stage III NSCLC after definitive chemoradiotherapy (CRT). However, whether durvalumab benefits patients with EGFR-mutated NSCLC remains unknown. METHODS: We conducted a multi-institutional retrospective analysis of patients with unresectable stage III EGFR-mutated NSCLC who completed concurrent CRT. Kaplan-Meier analyses evaluated progression-free survival (PFS) between patients who completed CRT with or without durvalumab. RESULTS: Among 37 patients, 13 initiated durvalumab a median of 20 days after CRT completion. Two patients completed 12 months of treatment, with five patients discontinuing durvalumab owing to progression and five owing to immune-related adverse events (irAEs). Of 24 patients who completed CRT without durvalumab, 16 completed CRT alone and eight completed CRT with induction or consolidation EGFR tyrosine kinase inhibitors (TKIs). Median PFS was 10.3 months in patients who received CRT and durvalumab versus 6.9 months with CRT alone (log-rank p = 0.993). CRT and EGFR TKI was associated with a significantly longer median PFS (26.1 mo) compared with CRT and durvalumab or CRT alone (log-rank p = 0.023). Six patients treated with durvalumab initiated EGFR TKIs after recurrence, with one developing grade 4 pneumonitis on osimertinib. CONCLUSIONS: In this study, patients with EGFR-mutated NSCLC did not benefit with consolidation durvalumab and experienced a high frequency of irAEs. Patients who initiate osimertinib after durvalumab may be susceptible to incident irAEs. Consolidation durvalumab should be approached with caution in this setting and concurrent CRT with induction or consolidation EGFR TKIs further investigated as definitive treatment.
Authors: Yufei Liu; Zhe Zhang; Waree Rinsurongkawong; Carl M Gay; Xiuning Le; Matthew S Ning; Jeff Lewis; Vadeerat Rinsurongkawong; J Jack Lee; Jack Roth; Stephen Swisher; Saumil Gandhi; Percy P Lee; Don L Gibbons; Ara A Vaporciyan; John V Heymach; Jianjun Zhang; Steven H Lin Journal: JAMA Netw Open Date: 2022-06-01
Authors: Josiah An; Melissa Yan; Nanmeng Yu; Adithya Chennamadhavuni; Muhammad Furqan; Sarah L Mott; Bradley T Loeffler; Timothy Kruser; Timothy L Sita; Lawrence Feldman; Ryan Nguyen; Mary Pasquinelli; Nasser H Hanna; Taher Abu Hejleh Journal: Transl Lung Cancer Res Date: 2021-08