Gérard Zalcman, MD, PhD, on Non–Small Cell Lung Cancer: Phase III Trial Findings on Nivolumab and Ipilimumab
ESMO Congress 2022
Gérard Zalcman, MD, PhD, of France’s Bichat-Claude Bernard Hospital, Assistance Publique–Hôpitaux de Paris, discusses phase III results from the IFCT-1701 trial, which explored the questions of whether to administer nivolumab plus ipilimumab for 6 months or whether to prolong the treatment in patients with advanced non–small cell lung cancer (Abstract 972O).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Currently there is no solid evidence to justify the duration of immunotherapy in the non-small cell lung cancer. In phase one trials, the duration was set without any limit until progression or toxicity. Then it was set to five years, then two years, but again, without randomized data to justify such duration.
The DICIPLE phase three trial, also entitled IFCT-1701, has had the goal to look whether a shorter duration of immunotherapy by Nivo plus Ipilimumab would be as efficient as a longer one, two years, in non-small cell lung cancer, in first-line setting.
So we randomized the non-small cell lung cancer patients, metastatic patients, PS01, aged 18 to 75, with measurable disease, any PDL1 into an induction treatment by Nivo plus Ipilimumab for six months at classical dosing. And at six months, we randomized patients with disease control into a continuation arm with the standard immunotherapy, or a stop-and-go arm, where the immunotherapy was stopped, the patient were observed, and the resume immunotherapy in case of progression. Of course, in the two arm, the follow up intervals were the same.
We accrued 265 patients, treated 261, but only randomized 71 patients because most of the patients progressed or exhibit toxicity precluding continuation. And unfortunately, we had to stop the trail because the Nivo plus Ipil combo will not be registered or nor reimbursed in Europe.
But, the results were striking because the median PFS in the continuation arm was 20.8 months, as compared with 35 months in the stop-and-go arm. The OS results show, again, there was no deleterious effect to stop early the immunotherapy, with 18 months OS rates of 79% in the continuation arm and 94% in the stop-and-go arm.
Furthermore, there were tenfold less grade three, four adverse events in the stop-and-go arm. So these results are hypothesis-generating because of the lack of statistical power, but are very provocative. And we have launched another randomized, phase three clinical trial with the very same design, meaning randomization at six months in patients with disease control, but after induction by chemo-immunotherapy. And again, it will be a non-inferiority trial. This trial is the DIAL trial, which began on March '22.
Jean-Pascal Machiels, MD, PhD, of Belgium’s Cliniques universitaires Saint-Luc (UCLouvain), discusses the primary results of the phase III KEYNOTE-412 study of pembrolizumab plus chemoradiation therapy (CRT) vs placebo plus CRT for patients with locally advanced head and neck squamous cell carcinoma (Abstract LBA5).
Christelle de la Fouchardiere, MD, of France’s Centre Léon Bérard, discusses phase III findings from the PRODIGE 65–UCGI 36–GEMPAX UNICANCER study, which evaluated whether the combination of gemcitabine and paclitaxel improves overall survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma after FOLFIRINOX failure or intolerance (Abstract LBA60).
Myriam Chalabi, MD, PhD, of The Netherlands Cancer Institute, discusses data from the NICHE-2 study, which confirms previously reported pathologic responses to short-term neoadjuvant nivolumab plus ipilimumab in patients with locally advanced mismatch repair–deficient colon cancer. Survival data suggest neoadjuvant immunotherapy may become standard of care and allow further exploration of organ-sparing approaches. (Abstract LBA7).
Neal D. Shore, MD, of Carolina Urologic Research Center/Genesis Care, discusses new data from the ENACT trial, which showed that patients with prostate cancer and the RNA biomarkers PAM50 and AR-A were likely to have better outcomes with enzalutamide treatment. The results suggest that such RNA biomarkers may help to identify patients who may benefit from enzalutamide treatment compared with active surveillance (Abstract 1385P).
Richard S. Finn, MD, of the Geffen School of Medicine at the University of California, Los Angeles, discusses primary phase III results from the LEAP-002 study of pembrolizumab, an anti–PD-1 therapy, plus lenvatinib, the orally available multiple receptor tyrosine kinase inhibitor, vs lenvatinib monotherapy in patients with advanced hepatocellular carcinoma (Abstract LBA34).