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.
Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute, and Laurence Albiges, MD, PhD, of France’s Gustave Roussy Cancer Centre, discuss phase III findings showing that cabozantinib in combination with nivolumab and ipilimumab reduced the risk of disease progression or death compared with the combination of nivolumab plus ipilimumab in patients with previously untreated advanced renal cell carcinoma of IMDC (the International Metastatic RCC Database Consortium) intermediate or poor risk. However, the combination of cabozantinib, nivolumab, and ipilimumab vs nivolumab plus ipilimumab did not demonstrate an overall survival benefit to patients (Abstract LBA8).
Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, discusses phase III results of the CheckMate 914 trial, which explored the efficacy of adjuvant nivolumab plus ipilimumab vs placebo in the treatment of patients with localized renal cell carcinoma who are at high risk of relapse after nephrectomy (Abstract LBA4).
Georgina V. Long, MD, PhD, of the Melanoma Institute Australia, discusses results from the CheckMate 915 trial, an analysis of the pretreatment circulating tumor DNA, along with other clinical and translational baseline factors, and their association with disease recurrence in patients with stage IIIB–D/IV melanoma treated with adjuvant immunotherapy (Abstract 788O).
Tony S.K. Mok, MD, of The Chinese University of Hong Kong, discusses two late-breaking abstracts presented at ESMO 2022: the phase II SUNRISE study, which compared sintilimab plus anlotinib vs platinum-based chemotherapy as first-line therapy in patients with metastatic non–small cell lung cancer (NSCLC); and the ORIENT-31 trial, which compared sintilimab with or without IBI305 (a bevacizumab biosimilar) plus chemotherapy in patients with EGFR-mutated nonsquamous NSCLC who experienced disease progression on EGFR tyrosine kinase inhibitors.
Matteo Lambertini, MD, PhD, of the University of Genova and Policlinico San Martino Hospital, talks about why oncofertility counseling should now be considered mandatory in the care of young women with breast cancer. Among the treatments he recommends offering are oocyte/embryo cryopreservation (or ovarian tissue cryopreservation in those not eligible for gamete cryopreservation); ovarian suppression with gonadotropin-releasing hormone agonist during chemotherapy; and long-term follow-up to improve the management of gynecology-related issues faced by these women.