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Published on: September 25, 2018
Neoadjuvant PD-1 and PD-L1 Blockade With Chemotherapy for Borderline Resectable and Unresectable Stage III Non-Small
Biagio Ricciuti1, Francesca Fusco2, Alissa Cooper3
1Lowe Center of Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Importance:
Patients with borderline resectable or unresectable stage III non-small cell lung cancer (NSCLC) with T4 and/or N2-N3 involvement face limited treatment options and poor outcomes. Neoadjuvant chemoimmunotherapy has shown promise in improving resectability and pathological responses.
Objective:
To evaluate the efficacy of neoadjuvant programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 (PD-L1) blockade combined with chemotherapy in enhancing surgical outcomes and pathological responses in patients with T4 and/or N2-N3 stage III NSCLC.
Design, Setting, And Participants:
This multicenter cohort study analyzed data from patients treated between February 2018 and January 2024 with neoadjuvant PD-1/PD-L1 inhibitors plus chemotherapy at academic and tertiary care centers across the US and Italy. Pathological and survival outcomes were assessed. Patients with stage III NSCLC and T4 and/or N2-N3 involvement were included. Data were collected from February 2018 to January 2024.
Exposures:
Neoadjuvant PD-1/PD-L1 blockade combined with platinum-based chemotherapy.
Main Outcomes And Measures:
Pathological complete response (pCR), major pathological response, surgical resectability, and event-free survival (EFS).
Results:
Of 112 patients, 58 (51.8%) were female, and the median (range) age was 66 (41-84) years. A total of 84(75.0%) underwent surgical resection, achieving a pCR rate of 29.0% (24 of 83 with available final pathology) and a major pathological response rate of 42.2% (35 of 83). Patients with both PD-L1 expression of 50% or more and high tumor mutational burden achieved the highest pCR rate (4 of 9 [44.4%]; P = .03). Conversely, covariants in KRAS/STK11 or KRAS/KEAP1 were associated with lack of pCR. Patients with single-station or multistation N2/N3 disease exhibited comparable pathological outcomes. The median EFS for all resected patients was 52.6 months (95% CI, 27.8 to not reached), and this was significantly longer in patients with pCR (not reached vs 27.8 months [95% CI, 19.5 to not reached]; P < .001).
Conclusions And Relevance:
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.
Insights
Neoadjuvant chemoimmunotherapy, combining PD-1/PD-L1 blockade with chemotherapy, significantly improves pathological response and resectability in advanced non-small cell lung cancer (NSCLC). This offers a promising treatment for patients with limited options.
Area of Science:
- Oncology
- Immunotherapy
- Thoracic Surgery
Background:
- Stage III non-small cell lung cancer (NSCLC) with T4 and/or N2-N3 involvement presents limited therapeutic options and poor prognoses.
- Neoadjuvant chemoimmunotherapy has emerged as a promising strategy to enhance resectability and pathological outcomes in these patients.
Purpose of the Study:
- To assess the efficacy of neoadjuvant programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 (PD-L1) blockade combined with chemotherapy.
- To evaluate improvements in surgical outcomes and pathological responses for patients with T4 and/or N2-N3 stage III NSCLC.
Main Methods:
- A multicenter cohort study analyzed data from 112 patients treated between February 2018 and January 2024.
- Patients received neoadjuvant PD-1/PD-L1 inhibitors plus platinum-based chemotherapy at academic and tertiary care centers in the US and Italy.
- Pathological and survival outcomes, including pathological complete response (pCR), major pathological response, and event-free survival (EFS), were assessed.
Main Results:
- 84% of patients underwent surgical resection, with a pCR rate of 29% and a major pathological response rate of 42.2%.
- Patients with PD-L1 expression ≥50% and high tumor mutational burden showed the highest pCR rate (44.4%).
- Event-free survival was significantly longer in patients achieving pCR (not reached vs. 27.8 months).
Conclusions:
- Neoadjuvant PD-1/PD-L1 blockade plus chemotherapy demonstrates high pathological response rates and surgical resectability in advanced NSCLC.
- This combination therapy represents a viable treatment option for borderline resectable or unresectable stage III NSCLC.
- Further validation through prospective studies is warranted to confirm these findings.
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