The phase II trial of neoadjuvant PD-1/PD-L1 blockade plus chemotherapy in borderline resectable and unresectable stage III NSCLC showed a significant improvement in event-free survival (EFS) with the combination (24.1 vs 10.6 months) compared to chemotherapy alone, with a hazard ratio (HR) of 0.62. Major pathological response rates were higher with immunotherapy (44.7% vs 22.3%), and no new safety signals were noted. The regimen improved surgical resection rates (68% vs 52%) without increasing perioperative complications. This validates chemoIO in the neoadjuvant setting particularly in whom we wish to pursue resection or avoid chemoradiation. It would be great to see this compared to chemoradiation followed by immunotherapy rather than chemotherapy alone.
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.
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.
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.
Neoadjuvant PD-1/PD-L1 blockade combined with platinum-based chemotherapy.
Pathological complete response (pCR), major pathological response, surgical resectability, and event-free survival (EFS).
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).
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.
Results showed the median event-free survival (EFS) was 54.8 months with nivolumab plus ipilimumab vs 20.9 months with chemotherapy. Three-year EFS rates were 56% vs 44%. Three-year overall survival (OS) rates were 73% vs 61% pathologic complete response rates were 20.4% vs 4.6%. This was three cycles of nivolumab and one dose of ipilimumab vs chemotherapy.
Dato showed a confirmed overall response rate (ORR) of 42.7% with a complete response (CR) of 4.3%. The median duration of response was 7.0 months, with a disease control rate of 86.3% and a median overall survival (OS) of 15.6 months. This could be another option for EGFR mutant patients who had multiple lines of therapy.
Patients were treated with thoracic and extrathoracic radiation to oligometastatic sites and it seems to help with improving survival, something to consider especially with SBRT now. Do our radiation oncologists have additional input?
Improved progression-free survival (PFS), now we have osimertinib and ramucirumab, amivantamab and Lazertinib (PFS 24.8 vs 23 months but NOT head to head).
Very thought-provoking review of immune checkpoint blockade therapy and strategies to possibly de-escalate therapy in the future. Could we reduce doses, extend dose intervals or diminish the duration of treatment? There is some (low-level) data supporting these ideas. However, ongoing prospective studies, mostly being done in countries with nationalized systems, will be informative on these topics. Expect interest in this topic to increase in a couple of years.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
