Vienna – The addition of neoadjuvant nivolumab (Opdivo) to chemotherapy significantly improved outcomes in patients with resectable stage IIIA-B non-small cell lung cancer, according to results from the NADIM II trial.
Combination therapy improved median progression-free survival (PFS) by 52% compared to chemotherapy alone (P=0.025) Puerta, Madrid, Spain The median follow-up was 26.1 months, Mariano Provencio, MD, of the de Hierro Hospital, reported at the plenary session of the World Congress on Lung Cancer (WCLC).
The 12-month PFS with nivolumab plus chemotherapy was 89.3% versus 60.7% with chemotherapy alone; at 24 months, the PFS was 66.6% and 43.3%, respectively.
Overall survival was 98.2% in the combination arm versus 82.1% in the chemotherapy arm at 12 months, and 84.7% and 63.4% at 24 months (HR 0.40, 95% CI 0.17-0.93, P=0.034).
“NADIM II confirms the superiority of neoadjuvant nivolumab plus chemotherapy in patients with resectable stage IIIA-B NSCLC,” Provencio said, adding that this is “the first A clinical trial of neoadjuvant immunotherapy-based resectable phase IIIA in combination with chemotherapy-B [NSCLC] to show improved overall survival.”
The trial recruited 20 academic centers from Spain Of the 90 patients, 86 were randomly assigned to one treatment group: 57 to receive nivolumab/chemotherapy and 29 to receive chemotherapy only. Its primary outcome, pathological complete response (pCR), was previously reported, showing a significant improvement with nivolumab plus chemotherapy (36.8% vs 6.9%, OR 7.88, 95% CI 1.70-36.51).
Additional results from NADIM II showed that all patients who achieved pCR were alive and disease-free at the time of data cutoff.
Regarding surgery, 53 of 57 patients (93%) in the nivolumab/chemotherapy group underwent surgery compared with 20 of 29 patients (69%) in the chemotherapy group. ) underwent surgery (OR 5.96, 95% CI 1.65-21.56). In addition, the proportion of patients undergoing R0 surgery was higher in the nivolumab/chemotherapy group, at 92.5%, compared with 65% in the chemotherapy group (OR 6.60, 95% CI 1.67-26.02).
“A problem with any neoadjuvant therapy is the proportion of patients whose disease progresses after neoadjuvant therapy, and the proportion of patients who do not undergo surgery,” commented Corinne Faivre-Finn, MD, University of Manchester, England , served as research discussant at WCLC meetings. “And the results in NADIM II were very favorable.”
However, Faivre-Finn pointed out that the study was conducted in a top academic center in Spain and asked: “So in reality world? Is there a risk of patients not having surgery or incomplete resection after chemotherapy/immunotherapy in the real world?”
NADIM II was used to validate the results of NADIM and the CHECKMATE 816 trial.
The Phase II NADIM trial was a single-arm trial evaluating neoadjuvant nivolumab plus chemotherapy. It showed higher survival and better pCR in patients with resectable stage IIIA NSCLC.
Phase III CheckMate 816 trial confirms NADIM findings, shown in
NADIM II is an open-label, phase II, multicenter clinical trial , including patients with resectable clinical stage IIIA NSCLC, ECOG performance status 0-1, and no known EGFR/ALK Change was randomized to receive nivolumab 360 mg plus paclitaxel 200 mg/m2 plus carboplatin AUC5 for three cycles, each 21 days as neoadjuvant therapy followed by surgery, or paclitaxel 200 mg/m 2 plus carboplatin AUC5 every 21 days for three cycles, Surgery is then performed.
Patients with R0 resection confirmed pathological assessment by starting adjuvant dosing of nivolumab within the third to eighth weeks after surgery and 6 months.
Baseline characteristics showed no statistically significant difference between the two groups according to Provencio.
Commenting on NADIM II, Faivre-Finn called the results impressive and agreed that they confirmed the CheckMate 816 findings. However, she also noted that overall survival was not the primary endpoint of the trial, and long-term overall survival data are needed to validate the impact of immunotherapy.
In addition, she noted that immunotherapy has success in the surgical treatment setting. “The time may be ripe for clinical trials comparing surgical versus non-surgical approaches to well integrate biomarkers for patient selection,” she said.
Mike Bassett is a staff writer specializing in oncology and hematology. He lives in Massachusetts.
This research was funded by Bristol-Myers Squibb.
Provencio reports on joint ventures with AstraZeneca, Roche, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Merck Sharp & Dohme, Takeda’s relationship and Thermo-Fisher.
Faivre-Finn reports relationships with AstraZeneca, Pfizer, Merck & Co and Elekta.