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.
Neoadjuvant immune checkpoint blockade with nivolumab plus ipilimumab improves overall survival (OS) in non–small cell lung cancer (NSCLC); however, randomized data for resectable lung cancer are limited. We report results from the exploratory concurrently randomized nivolumab plus ipilimumab and chemotherapy arms of the international phase III CheckMate 816 trial.
Adults with stage IB-IIIA (American Joint Committee on Cancer seventh edition) resectable NSCLC received three cycles of nivolumab once every 2 weeks plus one cycle of ipilimumab or three cycles of chemotherapy (on day 1 or days 1 and 8 of each 3-week cycle) followed by surgery. Analyses included event-free survival (EFS), OS, pathologic response, surgical outcomes, biomarker analyses, and safety.
A total of 221 patients were concurrently randomly assigned to nivolumab plus ipilimumab (n = 113) or chemotherapy (n = 108). At a median follow-up of 49.2 months, the median EFS was 54.8 months (95% CI, 24.4 to not reached [NR]) with nivolumab plus ipilimumab versus 20.9 months (95% CI, 14.2 to NR) with chemotherapy (HR, 0.77 [95% CI, 0.51 to 1.15]); 3-year EFS rates were 56% versus 44%. Higher rates of EFS events were initially seen, with later benefit favoring nivolumab plus ipilimumab; 3-year OS rates were 73% versus 61% (HR, 0.73 [95% CI, 0.47 to 1.14]); pathologic complete response rates were 20.4% versus 4.6%, respectively. In the respective arms, 83 (74%) and 82 patients (76%) underwent definitive surgery. Grade 3-4 treatment-related adverse events occurred in 14% and 36% of patients, respectively.
Neoadjuvant nivolumab plus ipilimumab showed potential long-term clinical benefit versus chemotherapy, despite early crossing of EFS curves in the preoperative phase and a lower rate of high-grade toxicity.
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.
Positive trial for the newest ADC on the block, Dato-DXd, is an ADC that delivers a topoisomerase I inhibitor payload via a TROP2 antibody. PFS was not impressive but favored DDxd at 4.4 vs 3.7 months in the docetaxel arm. This drug is now approved in metastatic breast cancer.
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.
