Neoadjuvant atezolizumab shrinks NSCLC tumors
SAN FRANCISCO – One-fifth of patients with resectable non–small cell lung cancer had a major pathologic response to neoadjuvant therapy with the immune checkpoint inhibitor atezolizumab (Tecentriq), according to a preliminary analysis of an ongoing phase 2 trial.
Among 45 patients evaluable for efficacy in theLCMC3 (Lung Cancer Mutation Consortium 3) trial, 10 (22%) had a major pathologic response (MPR), defined as a reduction in size to 10% or less of viable tumor cells, reported Filiz Oezkan, MD, from the Ohio State University, Columbus, and her colleagues.
“Immunophenotyping of peripheral blood showed significant immune subset changes after neoadjuvant atezolizumab treatment, and we also saw immune subset changes related to MPR and PD-L1 [programmed death–ligand 1] expression. Further study is needed on the biological role and of these immune cell changes in the context of clinical and pathological outcomes,” she said at the American Society of Clinical Oncology (ASCO) – Society for Immunotherapy of Cancer (SITC): Clinical Immuno-Oncology Symposium.
The investigators are continuing to enroll patients with resectable stage IB, II, IIA, or selected cases of stage IIIB resectable, previously untreated non–small cell lung cancer.
The patients receive two cycles of neoadjuvant atezolizumab 1,200 mg on days 1 and 22 prior to surgery. Following surgery, patients receive standard of care chemotherapy and adjuvant atezolizumab for up to 12 additional months.
Filiz Oezkan, MD
Dr. Oezkan presented safety data on the first 54 of 180 planned patients and efficacy data on 45 patients. The patients had a median age of 65 years, 29 of 54 (54%) were male, 35 (65%) had an Eastern Cooperative Oncology Group performance status of 0, and the remaining 19 had a performance status of 1.
A total of 35 patients had tumors with nonsquamous histology, and 19 had squamous tumors. The majority of patients had stage II or III disease. Only 4 patients had never used tobacco; the remaining 50 were either current or former smokers.
A total of 3 patients had a partial response to atezolizumab, and the remaining 42 in the efficacy analysis had stable disease according to Response Evaluation Criteria in Solid Tumors version 1.1.
As noted, 10 patients met the definition for having a major pathologic response.
In the safety population of 54 patients, 51 had (94%) an adverse event of any grade, and there was one sudden death deemed not to be treatment related in a patient who died about 2 weeks after surgery.
The most frequent treatment-related adverse events were grade 1 or 2 in severity including fatigue, anemia, arthralgia, elevated liver enzymes, pyrexia, diarrhea, nausea, decreased appetite, dyspnea, and infusion-related reactions.
Grade 3 or 4 treatment-related adverse events occurred in 3 patients, and serious adverse events occurred in 16. Two patients discontinued atezolizumab treatment because of adverse events, one for grade 1 pyrexia and one for grade 2 dyspnea.
Among all 54 patients, 31 had MPR assessment and paired pre- and postatezolizumab peripheral blood samples available for immune cell phenotyping, 31 had paired tumor samples at screen and surgery for PD-L1 staining, and 24 had screening samples available for whole exome sequencing.
In the immunophenotype analysis, the investigators saw significant increases in postatezolizumab CD8-positive T cells, mature natural killer (NK) cells, subsets of late-activated CD16- and CD56-positive NK cells, and CD16-positive–only NK cells, as well as an increase in a Th1 response–related dendritic cell subpopulation. In addition, they also saw a significant decrease in B cells.
Tissue PD-L1 status was available in samples from 23 of 31 patients. Of this group 16 had PD-L1-positive and 7 had PD-L1-negative tumors.
Patients with PD-L1-positive tumors had a significant decrease of senescent T cells and a monocytic myeloid cell subpopulation, as well as a significant increase in a Th1 response–related dendritic cells.
Among 31 patients evaluated for PD-L1 expression by immunohistochemistry, most had an increase in PD-L1-expressing immune cells after treatment.
Finally, the investigators found gene mutations in screening samples from 25 patients, with the most frequently mutated genes being TP53 and KRAS.
The study is supported by F. Hoffman–La Roche. Dr. Oezkan was supported by the Deutsche Forschungsgemeinschaft and a Merit Award from ASCO’s Conquer Cancer Foundation. She reported receiving honoraria from Novartis, consulting for Epigenomics, and receiving research funding and travel expenses from Genentech/Roche. Other coauthors reported similar relationships.
SOURCE: Oezkan F et al. ASCO-SITC, Abstract 99.
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