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Review
. 2024 Jul;118(1):119-129.
doi: 10.1016/j.athoracsur.2024.01.024. Epub 2024 Feb 3.

The Emerging Role of Immunotherapy in Resectable Non-Small Cell Lung Cancer

Elizabeth G Dunne  1 , Cameron N Fick  1 , James M Isbell  2 , Jamie E Chaft  3 , Nasser Altorki  4 , Bernard J Park  2 , Jonathan Spicer  5 , Patrick M Forde  6 , Daniel Gomez  7 , Puneeth Iyengar  7 , David H Harpole Jr  8 , Thomas E Stinchcombe  9 , Moishe Liberman  10 , Matthew J Bott  2 , Prasad S Adusumilli  2 , James Huang  2 , Gaetano Rocco  2 , David R Jones  11
Affiliations
Review

The Emerging Role of Immunotherapy in Resectable Non-Small Cell Lung Cancer

Elizabeth G Dunne et al. Ann Thorac Surg. 2024 Jul.

Abstract

Background: Despite surgical resection, long-term survival of patients with resectable non-small cell lung cancer (NSCLC) remains poor. Adjuvant chemotherapy, the standard of care for locally advanced NSCLC, provides a marginal 5.4% benefit in survival. Immune checkpoint inhibitors (ICIs) have shown a significant survival benefit in some patients with advanced NSCLC and are being evaluated for perioperative use in resectable NSCLC.

Methods: We conducted a literature search using the PubMed online database to identify clinical trials of immunotherapy in resectable NSCLC and studies analyzing biomarkers and immune priming strategies.

Results: Building on previous phase I and II trials, randomized phase III trials have shown efficacy of neoadjuvant nivolumab, perioperative pembrolizumab, adjuvant atezolizumab, and adjuvant pembrolizumab in the treatment of NSCLC with improvement of event-free/disease-free survival of 24% to 42%, leading to United States Food and Drug Administration approval of these drugs in the treatment of resectable NSCLC. Three additional phase III trials have also recently reported the use of immunotherapy both before and after surgery, with pathologic complete response rates of 17% to 25%, significantly better than chemotherapy alone. Perioperative ICI therapy has comparable perioperative morbidity to chemotherapy alone and does not impair surgical outcomes.

Conclusions: Perioperative immunotherapy, in combination with chemotherapy, is safe and improves outcomes in patients with resectable NSCLC. Questions regarding patient selection, the need for adjuvant ICI therapy after neoadjuvant chemoimmunotherapy, and the duration of perioperative immunotherapy remain to be answered by future trials.

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Conflict of interest statement

James M. Isbell has stock ownership in LumaCyte, consultant/advisory board member for AstraZeneca and Merck and receives institutional research support from Foresight, Guardant Health, Intuitive Surgical and Invitae.

Jaime Chaft serves as a consultant for AstraZeneca, Bristol-Myers Squibb, Flame Biosciences, Regeneron-Sanofi, Guardant Health and Arcus Biosciences and receives institutional research funding from AztraZeneca, Bristol-Myers Squibb, Merck and Novartis.

Nasser Altorki reports grant support from AstraZeneca and Janssen as well as a leadership role in Roche IMpower010 Steering Committee.

Bernard J. Park serves as a consultant for Intuitive Surgical, AstraZeneca, CEEVRA, and Medtronic.

Jonathan Spicer serves as a consultant for AstraZeneca, Merck, Roche, Bristol Myers Squibb, Novartis, Chemocentryx, Amgen, Protalix Biotherapeutics, Xenetic Biosciences, Regeneron, Eisai, as clinical trial leadership for Bristol Myers Squibb, Novartis, Roche, Merck, AstraZeneca and institutional grant support from AstraZeneca, Merck, Roche, CLS Therapeutics and Protalix Biotherapeutics.

Patrick M. Forde reports research grants to his institution from AstraZeneca, BMS, Novartis, Regeneron, BioNTech, consulting fees from Ascendis, AstraZeneca, BMS, Curevac, Novartis, Regeneron, G1, Genelux, Genentech, Gritstone, Merck, Janssen, F Star, Sanofi, Amgen, Fosun, Teva, Synthekine, Flame, Iteos, Tavotek, Teva and DSMB membership for Polaris.

Daniel Gomez reports research funding from Merck, AstraZeneca, Varian, and Bristol Myers Squibb and serves on the advisory boards of MedLearning Group, Medtronic, GRAIL, Johnson & Johnson, AstraZeneca, and Varian.

Puneeth Iyengar serves on the advisory board of AstraZeneca and institutional grant support from Incyte.

David Harpole serves as a speaker for and on the advisory board of AstraZeneca and is on the AEGEAN and MERMAID Executive Committees.

Tom Stinchombe is a consultant/advisory board member for Janssen Oncology, Genentech/Roche, Daiichi Sankyo/AstraZeneca, Takeda, Eisai/H3 Biomedicine, G1 Therapeutics, Spectrum Pharmaceuticals, Gilead Sciences, AstraZeneca, Coherus Biosciences, Abbvie, a DSMB membership for GlaxoSmithKline, Genetech/Roche, travel support from Pfizer, and institutional research support from AstraZeneca, SEagen, Mirati Therapeutics and Genentech/Roche

Moishe Liberman reports advisory relationship with Endocision, AssistIQ, Ditch Labs, Johnson &Johnson Lung Cancer Initiative, Noah Medical, Sparrow and research and educational grants from Boston Scientific, Olympus, Johnson & Johnson, Intuitive, Broncus, BMS, Merck, AstraZeneca, Pfizer, Roche, Novartis, POINT Biopharma, Galavanize Therapeutics, Caprion and ODS Medical.

Matthew J. Bott is a consultant for AstraZeneca.

Prasad S. Adusumilli declares research funding from ATARA Biotherapeutics; Scientific Advisory Board Member and Consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnston & Johnston, Orion pharma, Outpace Bio; Patents, royalties and intellectual property on mesothelin-targeted CAR and other T-cell therapies, which have been licensed to ATARA Biotherapeutics, issued patent method for detection of cancer cells using virus, and pending patent applications on PD-1 dominant negative receptor, wireless pulse-oximetry device, and on an ex vivo malignant pleural effusion culture system.

Gaetano Rocco has a financial relationship with Scanlan, AstraZeneca, and Medtronic.

David R. Jones serves as a consultant or speaker for or has received grant support from Merck, AstraZeneca, Genentech, More Health, and DAVA Oncology.

The other authors have no disclosures.

Figures

Figure 1.
Figure 1.
Comparison of radiographic response, surgical resection, major pathologic response, and pathologic complete response rates between neoadjuvant and perioperative trials. Chemo=chemotherapy; IO=immunotherapy; Ipi=ipilimumab; MPR=major pathologic response; Nivo=nivolumab; pCR=pathologic complete response.
Figure 2.
Figure 2.
Summary of treatment regimens in immunotherapy trials in resectable non-small cell lung cancer. Chemo=chemotherapy; SBRT=stereotactic body radiation therapy; SOC=standard of care.
See this image and copyright information in PMC

Comment in

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