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Cardiothoracic Surgery

Adjuvant Treatments for Surgically Resected Non–Small Cell Lung Cancer Harboring EGFR MutationsA Review

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JAMA Oncology

Published Online: May 11, 2023

Review

Article Information and Disclosures

Antonio Passaro, MD, PhD¹;

Tony S. K. Mok, MD²;

Ilaria Attili, MD¹;

Yi-Long Wu, MD³;

Masahiro Tsuboi, MD⁴;

Filippo de Marinis, MD¹;

Solange Peters, MD, PhD⁵

Author Affiliations

¹Division of Thoracic Oncology, European Institute of Oncology IRCCS, Milan, Italy
²State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Shatin, Hong Kong
³Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
⁴Division of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
⁵Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

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Abstract

Importance The use of adjuvant chemotherapy for stage IB-IIIA resected non–small cell lung cancer (NSCLC) has limited benefit for improving cure rates. The proportion of epidermal growth factor receptor (EGFR) alterations among patients with resected NSCLC is comparable to that observed in patients with advanced disease, and the use of EGFR tyrosine kinase inhibitors (TKIs) has been demonstrated to prolong disease-free survival (DFS). With recent approval of osimertinib in this context, a focus on the rapidly evolving scenario and future perspective in clinical practice is needed and was the aim of the current review.

Observations Randomized phase 3 clinical trials demonstrated DFS benefit with adjuvant EGFR TKI therapy in patients with resected EGFR mutation–positive NSCLC. The most recent trial (ADAURA) assessed 3-year adjuvant osimertinib and showed consistent DFS benefit and a significant role of the intervention in preventing the occurrence of brain metastasis. However, the role of adjuvant chemotherapy, the appropriate duration of treatment, the management of disease relapse, and the effective cure rate remain undetermined. A deeper investigation on molecular biomarkers, covariant patterns, and dynamic monitoring of postsurgical circulating DNA would be helpful for the implementation of future strategies to further improve survival rates after adjuvant therapy for EGFR mutation–positive NSCLC.

Conclusions and Relevance Adjuvant osimertinib revolutionized the treatment algorithm for patients with stage IB-IIIA resected EGFR mutation–positive NSCLC. Further evidence driven by clinical issues will be key for further optimization of the goals of adjuvant treatment in these patients.

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Article Information

Accepted for Publication: December 19, 2022.

Published Online: May 11, 2023. doi:10.1001/jamaoncol.2023.0459

Corresponding Author: Antonio Passaro, MD, PhD, Division of Thoracic Oncology, European Institute of Oncology IRCCS, Via G. Ripamonti 435, 20141 Milan, Italy (antonio.passaro@ieo.it).

Conflict of Interest Disclosures: Dr Passaro reported receiving personal fees for consulting from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche/Genentech, Mundipharma, and Daiichi Sankyo outside the submitted work. Dr Wu reported receiving grants from AstraZeneca and Bristol Myers Squibb; a grant to Guangdon Lung Cancer Institute from Pfizer; and personal fees for speaking from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Jiangsu Hengrui, MSD, Pfizer, Sanofi, and Roche outside the submitted work. Dr Tsuboi reported receiving personal fees and honoraria for lecturing from Johnson & Johnson Japan, Eli Lilly Japan, Taiho Pharmaceutical, Medtronic Japan, Ono Pharmaceutical Co, Ltd, Bristol Myers Squibb KK, and Teijin; personal fees and honoraria for lecturing and having a consulting or advisory role for AstraZeneca KK, Chugai Pharmaceutical Co, Ltd, MSD, and Novartis; and research grants from Boehringer Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical Co, Ltd, MSD, Bristol Myers Squibb KK, Novartis Research, and MiRXES outside the submitted work. Dr Peters reported receiving personal fees for serving on advisory councils and advisory boards to the institution from AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Illumina, Imedex, IQVIA, Incyte, Ipsen, iTeos, Janssen, Medscape, medtoday, Merck Sharp & Dohme, Merck Serono, Merrimack, Novartis, Novocure, OncologyEducation, PharmaMar, Phosplatin Therapeutics, PER, PeerView, Pfizer, Prime, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seagen, Takeda, and Vaccibody and personal fees for speaking to the institution from AiCME, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, GSK, Illumina, Imedex, Ipsen, Medscape, Merck Sharp & Dohme, Mirati, Novartis, PER, PeerView, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, and Takeda outside the submitted work. No other disclosures were reported.

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Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
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