{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:51:25Z","timestamp":1781675485748,"version":"3.54.5"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Resectable locally advanced EGFR-mutant non-small cell lung cancer (NSCLC) represents a distinct therapeutic challenge. Owing to an inherently immunosuppressive tumor microenvironment\u2014frequently characterized by absence of or low PD-L1 expression and sparse CD8+ tumor-infiltrating lymphocytes\u2014patients with EGFR alterations have been routinely excluded from landmark perioperative immunotherapy trials or have demonstrated negligible pathological responses. Consequently, the optimal neoadjuvant strategy for this population remains undefined, and the potential efficacy of immune checkpoint inhibitors combined with chemotherapy in selected EGFR-mutant subtypes is largely unexplored. We report two patients with resectable stage IIIA lung adenocarcinoma and concurrent high PD-L1 expression (tumor proportion score 60%) who achieved pathological complete response (pCR) following neoadjuvant chemoimmunotherapy. Case 1, a 60-year-old male harboring an EGFR exon 19 deletion, received three cycles of pemetrexed, carboplatin, and pembrolizumab, followed by R0 resection; postoperative adjuvant pembrolizumab was discontinued after one cycle because of grade 2 dizziness (CTCAE v5.0). Case 2, a 52-year-old female with an EGFR exon 21 L861Q missense mutation co-occurring with TP53 and PIK3CA alterations, exhibited primary resistance to afatinib with radiographic progression after one month. She subsequently underwent three cycles of pemetrexed, carboplatin, and sintilimab, achieving R0 resection with pCR, and declined further postoperative therapy. After 16 and 22 months of follow-up, respectively, the two patients remain disease-free. These cases suggest that for a specific subset of EGFR-mutant NSCLC\u2014particularly those with high PD-L1 expression and in whom targeted therapy has failed\u2014neoadjuvant chemoimmunotherapy may serve as a potent individualized strategy capable of overcoming pre-existing immune tolerance and inducing profound pathological responses. Nevertheless, this evidence remains strictly anecdotal; validation through large-scale, prospective, biomarker-driven clinical trials is imperative before any modification of standard clinical practice.<\/jats:p>","DOI":"10.3389\/fonc.2026.1844982","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:52:13Z","timestamp":1781671933000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Neoadjuvant chemoimmunotherapy achieving pathological complete response in two cases of stage III EGFR-mutant NSCLC with high PD-L1 expression"],"prefix":"10.3389","volume":"16","author":[{"given":"Diming","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oncology, Anhui Chest Hospital","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tangbin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Anhui Chest Hospital","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Anhui Chest Hospital","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, No.2 People\u2019s Hospital of Fuyang City","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1200\/JCO-25-00883","article-title":"Neoadjuvant osimertinib for resectable EGFR-mutated non-small cell lung cancer","volume":"43","author":"He","year":"2025","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2202170","article-title":"Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer","volume":"386","author":"Forde","year":"2022","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-2600(24)00269-8","article-title":"Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial","volume":"13","author":"Yue","year":"2025","journal-title":"Lancet Respir Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101615","article-title":"Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: phase 2 trial interim results (NEOTIDE\/CTONG2104)","volume":"5","author":"Zhang","year":"2024","journal-title":"Cell Rep Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-025-01061-7","article-title":"Treatment of NSCLC after chemoimmunotherapy - are we making headway","volume":"22","author":"Reck","year":"2025","journal-title":"Nat Rev Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(20)30140-6","article-title":"Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial","volume":"21","author":"Shu","year":"2020","journal-title":"Lancet Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-15-3101","article-title":"EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis","volume":"22","author":"Gainor","year":"2016","journal-title":"Clin Cancer Res Off J Am Assoc For Cancer Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.annonc.2023.10.052","article-title":"Perioperative pembrolizumab for early-stage non-small-cell lung cancer","volume":"389","author":"Wakelee","year":"2023","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01962-5","article-title":"Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial","volume":"28","author":"Chaft","year":"2022","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.02186","article-title":"Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer: updated results from the phase III randomized ADAURA trial","volume":"41","author":"Herbst","year":"2023","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.24735","article-title":"Perioperative toripalimab plus chemotherapy for patients with resectable non-small cell lung cancer: the Neotorch randomized clinical trial","volume":"331","author":"Lu","year":"2024","journal-title":"Jama"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1016\/j.jtcvs.2024.11.028","article-title":"Adjuvant immunotherapy does not improve survival in non-small cell lung cancer with major\/complete pathologic response after induction immunotherapy","volume":"169","author":"Zhao","year":"2025","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03577-y","article-title":"Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer","volume":"31","author":"Herbst","year":"2025","journal-title":"Nat Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.1779","article-title":"Circulating tumor DNA-guided de-escalation targeted therapy for advanced non-small cell lung cancer: a nonrandomized controlled trial","volume":"10","author":"Dong","year":"2024","journal-title":"JAMA Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2025.108592","article-title":"Induction therapy with dabrafenib, trametinib, and PD-1 inhibitor and surgical conversion in unresectable stage III non-small cell lung cancers with BRAF V600E mutation: 2 cases","volume":"205","author":"Cheng","year":"2025","journal-title":"Lung Cancer (Amsterdam Netherlands)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-025-00982-x","article-title":"Case report: a R0 resection successfully induced by T-DXd plus PD-1 inhibitor regimen in a primary unresectable stage IIIB NSCLC with ERBB2-mutation","volume":"9","author":"Zhang","year":"2025","journal-title":"NPJ Precis Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1844982\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:52:38Z","timestamp":1781671958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1844982\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":16,"alternative-id":["10.3389\/fonc.2026.1844982"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1844982","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]},"article-number":"1844982"}}