Researchers compared the percentage of non-viable tumor and tissue resident memory tumor infiltrating lymphocytes for nivolumab plus ipilimumab vs nivolumab alone.
CHICAGO–Neoadjuvant therapy with the immune checkpoint inhibitors nivolumab plus ipilimumab led to a higher percentage of non-viable tumor and tissue resident memory tumor infiltrating lymphocytes than nivolumab alone in patients with stage I to IIIA (single N2) resectable non–small-cell lung cancer (NSCLC). These are the findings of NEOSTAR, a phase II clinical trial (abstract 8504) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.
“We have a major unmet need for developing biomarkers for personalizing treatment in this area,” said Maximilian Diehn, MD, PhD, associate professor at Stanford, who served as a discussant during the session.
Previous studies have shown that monotherapy neoadjuvant treatment with immune checkpoint inhibitors leads to major pathologic response (MPR) rates (≤ 10% viable tumor at surgery) ranging from 22% to 45% in resected NSCLC, while combination therapies achieve 50% to 83% MPR rates.
In the study, 44 patients with stage I to IIIA (single N2) resectable NSCLC with a performance status of 0 to 1 were randomized to neoadjuvant nivolumab (3 mg/kg intravenously [IV] on days 1, 15, and 29) or nivolumab plus ipilimumab (1 mg/kg IV on day 1). Mean patient age was 66 years; 64% were male, 18% were never smokers, and 59% had adenocarcinomas. The patients had either stage IA (18%), stage IB (34%), stage IIA (16%), stage IIB (11%), and stage IIIA (20%).
A total of 39 patients went on to have surgery (11% not resected; 19% in the nivolumab group, 4% in the nivolumab/ipilimumab group). In addition, 25% of patients had an MPR or pathologic complete response.
Of the 37 patients who underwent resection and were evaluable, 30% had an MPR (nivolumab, 19%; nivolumab/ipilimumab, 44%). The nivolumab/ipilimumab group had a lower median percentage of viable tumor after treatment (20% vs 70%, P = .077). Objective response rate was 20% overall and similar in both arms. During surgery, 2 patients in the nivolumab group had broncopleural fistulas, and 5 in the nivolumab group experienced air leaks, as did 3 in the nivolumab/ipilimumab group.
More subjects in the nivolumab/ipilimumab group had higher CD3+ and CD103+ tissue-resident memory CD8+ tumor-infiltrating lymphocytes (CD3+: 81.2% vs 54.4%; P = .028; CD8+: 56.2% vs 38.3%; P = .069). Responders had a higher median pretreatment tumor programmed death ligand 1 (PD-L1) (80% vs 1%; P = .024), and patients with PD-L1 > 1% had a lower percentage of viable tumor than patients with PD-L1 ≤ 1% (median, 20% vs 80%, P = .046).
“PD-L1 expression may be the most obvious [biomarker], and it does seem to be associated with MPR, suggesting that just as in the adjuvant setting, PD-L1 does seem to correlate with response. Importantly, there are some patients who respond who are negative for this marker, so by itself it is not the perfect marker,” Diehn said.