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Neoadjuvant and Adjuvant Systemic Therapy for Early-Stage Non-small-Cell Lung Cancer

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Abstract

Approximately a third of patients with non-small-cell lung cancer (NSCLC) present with surgically resectable disease. Patients who undergo surgical resection are at a high risk of relapse, and neoadjuvant and adjuvant chemotherapy improves disease-free survival (DFS) and overall survival (OS). The outcomes with neoadjuvant and adjuvant chemotherapy are similar, and both are used in clinical practice. Recent trials investigated the role of immunotherapy and targeted therapy in patients with early-stage disease. A phase III trial of adjuvant atezolizumab compared with standard of care (SOC) in patients with resected stage II or III disease and PD-L1 expression of 1% or greater, and a second trial of adjuvant pembrolizumab compared with placebo in patients with stage IB–III (regardless of tumor proportion score PD-L1 expression), both demonstrated an improvement in DFS. In the neoadjuvant setting, results of a phase III trial of chemotherapy and nivolumab compared with chemotherapy alone revealed an improvement in pathological complete response rate and event-free survival in patients with stage IB–IIIA disease. Finally, for epidermal growth factor receptor (EGFR) mutant NSCLC, a phase III trial of osimertinib compared with SOC revealed an improvement in DFS. The results of these and ongoing trials illustrate the integration of immunotherapy and targeted therapies into the treatment paradigm of patients with surgically resected NSCLC and have led to FDA and EMA approvals in selected populations. Neoadjuvant trials have investigated novel endpoints such as major and complete pathological response, which have the potential to serve as surrogate endpoints for future trials.

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Authors and Affiliations

  1. Division of Medical Oncology, Duke Cancer Institute, Duke University Medical Center, DUMC 3841, Durham, NC, 27710, USA

    James Isaacs & Thomas E. Stinchcombe

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  1. James Isaacs
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  2. Thomas E. Stinchcombe
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Correspondence to James Isaacs.

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Conflicts of interest/competing interests

James Isaacs received salary support from Duke University of North Carolina Immunotherapy T32 Training Program, and has received honoraria from MJH Life Sciences Participation in Clinical Congress Consultants, and ASCO panel review for oncology fellows. Thomas E. Stinchcombe has received honorarium from participation in advisory boards from Takeda, AstraZeneca, Genentech/Roche, Foundation Medicine, Pfizer, EMD Serono, Novartis, Daiichi Sankyo¸ Lilly, Medtronic, Puma Biotechnology, Janssen Oncology, Regeneron, Turning Point Therapeutics, Sanofi/Aventis, and has received grant support for clinical trials from Genentech/Roche, AstraZeneca, Takeda, Advaxis, Regeneron, and Mirati.

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JI contributed to the conceptualization, investigation, and writing (original draft, review and editing) and TS contributed to the conceptualization, investigation, and writing (original draft, review and editing).

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Isaacs, J., Stinchcombe, T.E. Neoadjuvant and Adjuvant Systemic Therapy for Early-Stage Non-small-Cell Lung Cancer. Drugs 82, 855–863 (2022). https://doi.org/10.1007/s40265-022-01721-3

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