Case Report: Neoadjuvant chemoimmunotherapy achieving pathological complete response in two cases of stage III...

Resectable locally advanced EGFR-mutant non-small cell lung cancer (NSCLC) represents a distinct therapeutic challenge. Owing to an inherently immunosuppressive tumor microenvironment-frequently characterized by absence of or low PD-L1 expression and sparse CD8+ tumor-infiltrating lymphocytes-patients 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-particularly those with high PD-L1 expression and in whom targeted therapy has failed-neoadjuvant 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.