TY - JOUR
T1 - Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC
T2 - A Multicenter Retrospective Cohort Study
AU - Nassar, Amin H.
AU - Kim, So Yeon
AU - Aredo, Jacqueline V.
AU - Feng, Jamie
AU - Shepherd, Frances
AU - Xu, Chao
AU - Kaldas, David
AU - Gray, Jhanelle E.
AU - Dilling, Thomas J.
AU - Neal, Joel W.
AU - Wakelee, Heather A.
AU - Liu, Yufei
AU - Lin, Steven H.
AU - Abuali, Tariq
AU - Amini, Arya
AU - Nie, Yunan
AU - Patil, Tejas
AU - Lobachov, Anastasiya
AU - Bar, Jair
AU - Fitzgerald, Bailey
AU - Fujiwara, Yu
AU - Marron, Thomas U.
AU - Thummalapalli, Rohit
AU - Yu, Helena
AU - Owen, Dwight H.
AU - Sharp, John
AU - Farid, Saira
AU - Rocha, Pedro
AU - Arriola, Edurne
AU - D'Aiello, Angelica
AU - Cheng, Haiying
AU - Whitaker, Ryan
AU - Parikh, Kaushal
AU - Ashara, Yash
AU - Chen, Luxi
AU - Sankar, Kamya
AU - Harris, Jeremy P.
AU - Nagasaka, Misako
AU - Ayanambakkam, Adanma
AU - Velazquez, Ana I.
AU - Ragavan, Meera
AU - Lin, Jessica J.
AU - Piotrowska, Zofia
AU - Wilgucki, Molly
AU - Reuss, Joshua
AU - Luders, Heike
AU - Grohe, Christian
AU - Baena Espinar, Javier
AU - Feiner, Ella
AU - Punekar, Salman R.
AU - Gupta, Shruti
AU - Leal, Ticiana
AU - Kwiatkowski, David J.
AU - Mak, Raymond H.
AU - Adib, Elio
AU - Naqash, Abdul Rafeh
AU - Goldberg, Sarah B.
N1 - Publisher Copyright:
© 2024
PY - 2024
Y1 - 2024
N2 - Introduction: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown. Methods: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022. Kaplan-Meier method was used to estimate real-world progression-free survival (rwPFS, primary end point) and overall survival (secondary end point). Treatment-related adverse events (trAEs) during consolidation treatment were defined using Common Terminology Criteria for Adverse Events version 5.0. Multivariable Cox regression analysis was used. Results: Of 136 patients with stage III EGFRmut NSCLC treated with definitive concurrent CRT, 56 received consolidation durvalumab, 33 received consolidation osimertinib, and 47 was on observation alone. Baseline characteristics were similar across the three cohorts. With a median follow-up of 46 months for the entire cohort, the median duration of treatment was not reached (NR) for osimertinib (interquartile range: NR–NR) and was 5.5 (interquartile range: 2.4–10.8) months with durvalumab. After adjusting for nodal status, stage III A/B/C, and age, patients treated with consolidation osimertinib had significantly longer 24-month rwPFS compared to those treated with durvalumab or in the observation cohorts (osimertinib: 86%, durvalumab: 30%, observation: 27%, p < 0.001 for both comparisons). There was no difference in rwPFS between the durvalumab and the observation cohorts. No significant difference in overall survival across the three cohorts was detected, likely due to the limited follow-up. Any-grade trAE occurred in 52% (2 [6.1%] grade ≥3) and 48% (10 [18%] grade ≥3) of patients treated with osimertinib and durvalumab, respectively. Of 45 patients who progressed on consolidation durvalumab, 37 (82%) subsequently received EGFR tyrosine kinase inhibitors. Of these, 14 (38%) patients developed trAEs including five patients with pneumonitis (14%; 2 [5.4%] grade ≥3) and five patients with diarrhea (14%; 1 [2.7%] grade ≥3). Conclusions: This study suggests that among patients with stage III unresectable NSCLC with a sensitizing EGFR mutation, consolidation osimertinib was associated with a significantly longer rwPFS compared to durvalumab or observation. No unanticipated safety signals were observed with consolidation osimertinib.
AB - Introduction: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown. Methods: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022. Kaplan-Meier method was used to estimate real-world progression-free survival (rwPFS, primary end point) and overall survival (secondary end point). Treatment-related adverse events (trAEs) during consolidation treatment were defined using Common Terminology Criteria for Adverse Events version 5.0. Multivariable Cox regression analysis was used. Results: Of 136 patients with stage III EGFRmut NSCLC treated with definitive concurrent CRT, 56 received consolidation durvalumab, 33 received consolidation osimertinib, and 47 was on observation alone. Baseline characteristics were similar across the three cohorts. With a median follow-up of 46 months for the entire cohort, the median duration of treatment was not reached (NR) for osimertinib (interquartile range: NR–NR) and was 5.5 (interquartile range: 2.4–10.8) months with durvalumab. After adjusting for nodal status, stage III A/B/C, and age, patients treated with consolidation osimertinib had significantly longer 24-month rwPFS compared to those treated with durvalumab or in the observation cohorts (osimertinib: 86%, durvalumab: 30%, observation: 27%, p < 0.001 for both comparisons). There was no difference in rwPFS between the durvalumab and the observation cohorts. No significant difference in overall survival across the three cohorts was detected, likely due to the limited follow-up. Any-grade trAE occurred in 52% (2 [6.1%] grade ≥3) and 48% (10 [18%] grade ≥3) of patients treated with osimertinib and durvalumab, respectively. Of 45 patients who progressed on consolidation durvalumab, 37 (82%) subsequently received EGFR tyrosine kinase inhibitors. Of these, 14 (38%) patients developed trAEs including five patients with pneumonitis (14%; 2 [5.4%] grade ≥3) and five patients with diarrhea (14%; 1 [2.7%] grade ≥3). Conclusions: This study suggests that among patients with stage III unresectable NSCLC with a sensitizing EGFR mutation, consolidation osimertinib was associated with a significantly longer rwPFS compared to durvalumab or observation. No unanticipated safety signals were observed with consolidation osimertinib.
KW - Adverse events
KW - Chemotherapy
KW - Durvalumab
KW - EGFR
KW - Non–small cell lung cancer
KW - Osimertinib
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85186574736&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85186574736&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2024.01.012
DO - 10.1016/j.jtho.2024.01.012
M3 - Article
C2 - 38278303
AN - SCOPUS:85186574736
SN - 1556-0864
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
ER -