KEY TAKEAWAYS
- The phase 3 trial assessed whether 6-months nivo/ipi duration was equivalent to continuation until progression in patients with aNSCLC and no targetable mutation.
- Eligible patients were treatment-naive, age>18, PS 0-1, and had histologically proven stage IV NSCLC and measurable disease. They received Nivo 3 mg/kg q2w plus Ipi 1 mg/kg q6w until progression or unacceptable toxicity.
- The study did not reach its primary endpoint, with a median PFS of 20.8 months in arm A and not reached in arm B patients, and 12-month PFS of 57.1% and 77.6% in arm A and B, respectively (p=0.09).
- The premature halt of the trial resulted in underpowered data to detect a significant difference in PFS and immature data on overall survival.
Patients (pts) with advanced non-small cell lung cancer (aNSCLC) and no targetable mutation are typically treated with 1st-line immunotherapy (io). The traditional two-year io time frame is not supported by evidence. Researchers wanted to see if, in patients with stable disease, six months of nivo/ipi was the same as continuing until progression. Patients with histologically confirmed stage IV NSCLC and disease control (DC) were eligible for inclusion in this multicenter, randomized, non-inferiority phase III trial. Until progression or intolerable toxicity occurred, they were given Nivo 3 mg/kg q2w and Ipi 1 mg/kg q6w. Patients with DC who had not experienced any severe TRAEs were randomly assigned (1:1) to either arm A, io continuation, or arm B, observation, after 6 months. Patients in Arm A received a platinum-based second-line chemotherapy of the investigator’s choosing upon progression, while those in Arm B returned to double io. The primary outcome measure was time to progression. To get 80% power with a 0.025 standard deviation error, researchers needed to assign 900 points 450 pts x 2 randomly. The trial’s steering committee saw that the European filing for the io combo was missing and made the call to halt accrual on January 15th, 2021.
There were 265 pts accrued between May 2018 and January 2021; 70.6% were male, the median age was 62.7 years old, 60% were in stage IVB, 22.3% had SCC, 9.9% had PDL1≥50%, and 12.2% had PDL1<1%. At the 6-month mark, 137 (72.1%) of patients had experienced disease progression; 11 (5.8%) had died; 29 (15.3%) had experienced TRAEs contraindicating continuation; and 13 (6.8%) were deemed ineligible for randomization. Researchers randomized 71 DC patients. Median progression-free survival (PFS) was 20.8 (8.3-NR) months in arm A and not reached (17.7-NR) in arm B pts after a median follow-up of 21.0 months from randomization. Survival rates at 12 months for patients in arm A were 57.1% (39.3-71.5) and 77.6% (58.7-88.7) (p=0.09), respectively. Arm B had a lower adjusted hazard ratio than arm A by 0.65 (95% CI, 0.22-1.49), p=0.31. Young data on OS do not indicate a clear winner (adjusted HR, arm B vs A: 0.52 95%CI (0.13-2.12), p=0.36). The frequency of iTRAES grades G3-5 did not differ significantly. Since data are underpowered due to the trial’s premature halt, the non-significant PFS difference between the 6-month and the continuation arms generates hypotheses.
Source: https://oncologypro.esmo.org/meeting-resources/esmo-congress/nivolumab-nivo-plus-ipilimumab-ipi-6-months-treatment-versus-continuation-in-patients-with-advanced-non-small-cell-lung-cancer-ansclc-result
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03469960
G. Zalcman, A. Madroszyk Flandin, O. Molinier, C. DAYEN, T. Egenod, D. Debieuvre, S. BEAUCAIRE-DANEL, A. Dixmier, E. Pichon, S. Galland Girodet, E. Giroux-Leprieur, N. Cloarec, J. Cadranel, J. Otto, P. Romand, A. Langlais, F. Morin, M. Antoine, V. Westeel, A.C. Toffart/972O – Nivolumab (Nivo) plus ipilimumab (Ipi) 6-months treatment versus continuation in patients with advanced non-small cell lung cancer (aNSCLC): Results of the randomized IFCT-1701 phase III trial/Annals of Oncology (2022) 33 (suppl_7): S448-S554. 10.1016/annonc/annonc1064
