Adding ipilimumab to nivolumab and chemotherapy improves responses in patients with operable non-small cell lung cancer (NSCLC), according to phase 2 results published in Nature Medicine.
Patients who received ipilimumab plus nivolumab and chemotherapy had a higher major pathologic response (MPR) rate than patients who received nivolumab and chemotherapy only. However, event-free survival (EFS) and overall survival (OS) outcomes were similar between the treatment arms.
This phase 2 trial (NEOSTAR, ClinicalTrials.gov Identifier: NCT03158129) enrolled patients with stage IB-IIIA NSCLC. They were randomly assigned to receive nivolumab and chemotherapy (standard care, n=22) or ipilimumab plus nivolumab and chemotherapy (n=22).
The median age was 69.5 years in the standard care arm and 63.1 years in the ipilimumab arm. In both arms, 77% of patients had non-squamous NSCLC. In the standard care arm, 50% of patients each had stage IB/II disease or stage IIIA disease. In the ipilimumab arm, 41% of patients had stage IB/II disease, and 59% had stage IIIA disease.
The primary endpoint was MPR rate, which was 50% in the ipilimumab arm and 32.1% in the standard care arm. The pathologic complete response (pCR) rate was 18.2% in both arms.
In patients without known EGFR/ALK alterations, the MPR rate was 41.2% in the standard care arm and 62.5% in the ipilimumab arm. The pCR rates were 23.5% and 25%, respectively.
All patients assigned to standard care underwent resection, and the R0 resection rate was 90%. In the ipilimumab arm, 91% of patients underwent resection, and the R0 resection rate was 95%. The 30-day and 90-day mortality rates were 0% in both arms.
The median follow-up was 39.2 months in the standard care arm and 24.0 months in the ipilimumab arm. The median EFS and OS were not reached in either arm.
The 12-month EFS rate was 96% in the standard care arm and 82% in the ipilimumab arm. The 24-month EFS rate was 73% and 77%, respectively.
The 12-month OS rate was 100% in the standard care arm and 91% in the ipilimumab arm. The 24-month OS rate was 91% in both arms.
The incidence of grade 3-4 treatment-related adverse events (TRAEs) was 45% in the standard care arm and 20% in the ipilimumab arm.
The most common grade 3-4 TRAEs in the standard care arm were hyponatremia (14%), white blood cell count decrease (14%), and febrile neutropenia (14%). The most common grade 3-4 TRAE in the ipilimumab arm was anemia (14%).
“The dual immune checkpoint therapy plus CT [chemotherapy] produces numerically higher MPR rates, is overall safe and tolerated, enhances anti-tumor immune activity, and mitigates an immunosuppressive phenotype in exploratory analyses,” the researchers concluded. “The addition of CTLA-4 blockade to PD-(L)1 inhibition plus CT deserves further investigation for patients with resectable NSCLC.”
Disclosures: This research was supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Cascone T, Leung CH, Weissferdt A, et al. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: The phase 2 platform NEOSTAR trial. Nat Med. Published online March 16, 2023. doi:10.1038/s41591-022-02189-0