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Neoadjuvant PD-1/PD-L1 Inhibition Plus Chemotherapy in Borderline-Resectable or Unresectable Stage III NSCLC


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In a retrospective cohort study reported in JAMA Oncology, Ricciuti et al examined whether neoadjuvant PD-1/PD-L1 inhibition plus platinum-based chemotherapy showed activity in patients with borderline-resectable/unresectable stage III non–small cell lung cancer (NSCLC).

Study Details

The study involved 112 patients with stage III disease with T4 and/or N2–N3 involvement consecutively enrolled between February 2018 and January 2024 at Dana-Farber Cancer Institute, Boston; Memorial Sloan Kettering Cancer Center, New York; and Regina Elena Cancer Center, Rome. A total of 51.8% of patients were female, and the median patient age was 66 years (range, 41–84 years). Outcome measures were pathologic complete response (pCR), major pathologic response, surgical resectability, and event-free survival.

Key Findings

Of 112 patients, 84 (75.0%) underwent surgical resection, with a pCR rate of 29.0% (24 of 83 with available final pathology) and a major pathologic response rate of 42.2% (35 of 83 with final pathology). In four of nine patients (44.4%) with both PD-L1 ≥ 50% and a high tumor mutational burden, pCR was achieved (P = .03). Covariants in KRAS/STK11 or KRAS/KEAP1 were associated with a lack of pCR. Patients with single-station or multistation N2 or N3 disease had comparable pathologic outcomes.

Median event-free survival among all resected patients was 52.6 months (95% confidence interval [CI] = 27.8 months to not reached). Median event-free survival was not reached in patients with pCR vs 27.8 months (95% CI = 19.5 months to not reached) in those without pCR (P < .001).

The investigators concluded: “In this study, neoadjuvant PD-1/PD-L1 blockade combined with chemotherapy resulted in high pathological response rates and surgical resectability in patients with T4 and/or N2–N3 stage III NSCLC. This approach offers a viable treatment option for patients with borderline resectable or unresectable NSCLC but requires further validation through prospective studies.”

Biagio Ricciuti, MD, PhD, of Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, is the corresponding author of the JAMA Oncology article.

Disclosure: For full disclosures of all study authors, visit JAMA Oncology.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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