There is no firm rational for the duration of immunotherapy in lung cancer. Initially, this duration was set with no limit until progression and toxicity, then it was set to five years, then two years, but again, without firm randomized data. So the DICIPLE IFCT 1701 phase III trial aimed to look whether a six-month duration could do as good as a long duration of two years of immunotherapy with less toxicity. This was a non-inferiority phase III trial aimed to accrue more than 800 patients, but it was terminated early because the combination nivo plus ipilimumab won't be registered, nor reimbursed in Europe. We accrued 265 patients, 71 were randomized into a standard arm, which is the continuation of nivo plus immunotherapy for two years, or an experimental arm, which is to stop at six months only for patients with disease control to observe these patients and to resume immunotherapy in case of a relapse. The result are striking because the median PFS in the continuation arm is 20.8 months versus 35 months in the experimental arm, and the OS results are consistent with the PFS. But the most striking finding is that we were able to lower the incidence of grade III/IV immune-related adverse events by tenfold in the experimental arm. We accrue non cell lung cancer patient with stage IV, meaning metastatic patients, PS01 with measurable disease, age 18 to 75 years old, any PDL1 level of expression in the tumor. What shows this trial is that by decreasing the length of treatment, of immunotherapy treatment, it's logical to decrease the incidence of grade III/IV immune-related adverse events. So it's a way to explore in future trial, and this is the reason why another trial with the very same design has been launched, but after induction by chemo immunotherapy, and I firmly think that patient with major responses do not deserve longer treatment and is a way to decrease the incidence of immune-related toxicity, which could be life-threatening and alter quality of life.
