|The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Results of a randomized study of patients with resectable non-small cell lung cancer (NSCLC) treated with the anti-programmed cell death-1 (PD-1) antibody, nivolumab, or the combination of nivolumab with the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibody, ipilimumab, in the neoadjuvant setting suggested that clinical responses were higher with the latter regimen. The findings from this study were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.
Although there is evidence that neoadjuvant immune checkpoint inhibitor (ICI) therapy is associated with achievement of relatively high rates of major pathologic response (major pathologic response [MPR]; ≤10% viable tumor) in patients with resectable NSCLC, additional studies are needed to more fully optimize treatment selection in this setting, as well to evaluate clinical outcomes in the context of biomarkers of response for patients receiving these treatments.
Two arms of the randomized, open-label, phase 2 NEOSTAR study (ClinicalTrials.gov Identifier: NCT03158129) involved preoperative treatment of adult patients with stage I to stage IIIA resectable NSCLC with either single-agent nivolumab, or the combination of nivolumab and ipilimumab followed by surgical resection. The primary end point of this study was rate of MPR. Secondary study end points included overall response rate (ORR) to induction immunotherapy by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. In addition, tumor expression of programmed cell death-ligand 1 (PD-L1), as well as tumor immune infiltrates, were assessed in biopsies obtained before and after neoadjvuant therapy using immunohistochemistry and flow cytometry, respectively.
Of the 44 patients randomly assigned to these treatment arms, 23 and 21 received nivolumab alone or combination therapy, respectively. Clinicopathologic characteristics of these patients included a mean patient age of 65.6 years, disease histology characterized by adenocarcinoma in 59% of patients, and stage IA/B and stage IIIA disease in 52% and 20% of patients, respectively.
In the intention-to-treat (ITT) population (44 patients), MPR was 17% and 33% for patients receiving single-agent versus combination ICI therapy, with an overall MPR of 25%. Seven patients in the combination arm achieved a pathologic complete response.
Thirty-seven patients (84%) in the overall group underwent surgery on trial. In the surgery subgroup, the MPR was 19% (with pCR in 2 patients) for patients receiving nivolumab monotherapy and 44% (with pCR in 6 patients) for those receiving combination therapy, with an overall MPR of 30%.
The ORR in the overall group was 20%, with 1 complete response in a patient receiving combination therapy, and only 14% of patients experiencing progressive disease. Respective ORRs for the monotherapy and combination therapy arms were 22% and 19%.
Interestingly, apparent radiographic progression of disease localized to lymph nodes was noted in 11% of patients following neoadjuvant immune checkpoint inhibitor therapy, although subsequent pathologic assessment of the nodes revealed granulomas but no evidence of disease in those treated with combination therapy.
“This phenonenon, which we named ‘nodal flare’ is of great importance,” the presenter noted, since potentially curative surgery may be unnecessarily withheld if it is not distinguished from true disease progression.
Adverse events were considered to be acceptable, with 4 grade 3 to grade 5 treatment-related adverse events reported.
Regarding potential biomarkers of response to neoadjuvant immune checkpoint inhibitor therapy, pretreatment expression levels of PD-L1 were significantly higher in patients achieving radiologic and pathologic measures of complete response compared with patients not achieving 1 or both of these response measures (P =.015).
In addition, the combination of nivolumab plus ipilimumab was associated with increased T-cell infiltration, diversity and reactivity, and with increased frequencies of tissue resident and effector memory T cells at surgery compared with nivolumab alone.
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Cascone T, William WN, Weissferdt A, et al. Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): Clinical and correlative results from the NEOSTAR study. 2019 American Association of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 8504.