Targeted treatment for unresectable EGFR mutation-positive stage III non-small cell lung cancer: Emerging evidence and future perspectives.

Epidermal growth factor receptor (EGFR) mutations are detected in up to one third of patients with unresectable stage III non-small cell lung cancer (NSCLC). The current standard of care for unresectable stage III NSCLC is consolidation durvalumab for patients who have not progressed following concurrent chemoradiotherapy (the 'PACIFIC regimen'). However, the benefit of immunotherapy, specifically in patients with EGFR mutation-positive (EGFRm) tumors, is not well characterized, and this treatment approach is not recommended in these patients, based on a recent ESMO consensus statement. EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated significant improvements in patient outcomes in EGFRm metastatic NSCLC. The benefits of these agents have also translated to patients with EGFRm early-stage resectable disease as adjuvant therapy. The role of EGFR-TKIs has yet to be prospectively characterized in the unresectable setting. Preliminary efficacy signals for EGFR-TKIs in unresectable EGFRm stage III NSCLC have been reported from a limited number of subgroup and retrospective studies. Several clinical trials are ongoing assessing the safety and efficacy of EGFR-TKIs in this patient population. Here, we review the current management of unresectable EGFRm stage III NSCLC. We outline the rationale for investigating EGFR-TKI strategies in this setting and discuss ongoing studies. Finally, we discuss the evidence gaps and future challenges for treating patients with unresectable EGFRm stage III NSCLC.

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Déclaration de conflit d'intérêts

Declaration of competing interest Terufumi Kato reports consulting/advisory roles: AstraZeneca, BeiGene, Daiichi-Sankyo, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer; honoraria: Amgen Inc., AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai Pharmaceuticals Co., Ltd., Daiichi-Sankyo, Eli Lilly and Company, GlaxoSmithKline, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical Co., Ltd., Pfizer, Taiho Pharmaceutical, Takeda; employment (spouse): Eli Lilly and company; research support (to institution): AbbVie Inc., Amgen Inc., AstraZeneca, BeiGene, Blueprint Medicines, Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Eli Lilly and Company, HaiHe Biopharma, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., Takeda, Turning Point Therapeutics Inc. Ignacio Casarini reports local principal investigator role: AstraZeneca, Bristol-Myers Squibb, Exelixis, Lilly, Merck Sharp & Dohme, Novartis, Roche (non-financial and for institution); principal investigator role for multiple clinical studies: AstraZeneca, Bristol-Myers Squibb, Exelixis, Lilly, Merck Sharp & Dohme, Novartis; principal investigator role for one clinical study: Roche. Corinne Faivre-Finn reports research funding: AstraZeneca, and Elekta; travel expenses: AstraZeneca, Elekta, Peter MacCallum Cancer Centre, and CF-F’s institution; and uncompensated relationships: AstraZeneca, Elekta, and Merck Sharpe & Dohme. CF-F is supported by a grant from the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre. Fiona Hegi-Johnson reports research funding: AstraZeneca; honoraria: AstraZeneca; payment or honoraria for lectures and presentations: BeiGene, Merck Sharpe & Dohme. Participation on an advisory board: AstraZeneca. FH-J is supported by the Victorian Cancer Agency. Shun Lu reports consulting/advisory roles: AstraZeneca, Boehringer Ingelheim, GenomiCare Biotechnology, Hutchison MediPharma Ltd., Pfizer, prIME Oncology, Roche, Simcere Pharmaceutical Group, Yuhan, Zai Lab; speaker’s bureau: AstraZeneca, Hansoh Pharmaceutical Group Co. Ltd., Hengrui Pharmaceuticals Company Ltd., Roche; research funding (to institution): AstraZeneca, BeiGene, Bristol-Myers Squibb, Hansoh Pharmaceutical Group Co. Ltd., Hengrui Pharmaceuticals Company Ltd., Hutchison MediPharma Ltd., Lilly Suzhou Pharmaceutical Co. Ltd., Roche. Mustafa Özgüroğlu reports consulting/advisory roles: Astellas (to self and institution), Janssen, Sanofi; honoraria: Astellas (to self and institution), Janssen, Novartis, Roche, Sanofi. Suresh S. Ramalingam reports consulting/advisory roles: Amgen Inc., AstraZeneca, Bristol-Myers Squibb, Genentech, Merck & Co. Inc., Takeda Inc., Tesaro; research funding: Amgen Inc., Advaxis Inc., AstraZeneca, Bristol-Myers Squibb, Genmab, Merck & Co. Inc., Takeda, Tesaro Inc. Manuel Cobo declares no conflicts of interest.