Lung cancer is the most common cancer in the world and the leading cause of cancer-related deaths in Western countries. Unfortunately, at the time of diagnosis, the majority of patients already have metastatic disease and a systemic, palliative treatment is the primary therapeutic option. Guidelines for PS 2 patients or older than 75 years old patients at the time of diagnosis recommend for fit patients a carboplatin doublet chemotherapy. Nivolumab has proven efficacy in 3rd line squamous cell lung carcinoma and is superior to chemotherapy in 2nd line treatment of squamous and non-squamous lung cancer in term of overall survival. In 1st line, nivolumab failed to show superiority compared to a platin based doublet in terms of progression free survival and overall survival in tumors ≥ 5% PD-L1 expression. The association Nivolumab plus Ipilimumab showed encouraging results in first line setting in phase 1 study. The investigators think that with regard to the manageable toxicity of nivolumab in lung cancer population and the possibility to obtain long responses, this association could be a valid option for this population of elderly and/or PS2 patients in term of overall survival.
Name: Nivolumab + Ipilimumab
Description: Nivolumab dosed intravenously over 30 minutes at 240 mg every 2 weeks combined with Ipilimumab dosed intravenously over 30 minutes at 1 mg/kg every 6 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol.Type: DrugNivolumab + Ipilimumab
Name: Chemotherapy
Description: Doublet of chemotherapy according to standard of care carboplatin (AUC 5) with a dose that will be capped to 700 mg and pemetrexed (500 mg/m²) over 4 to 6 hours every three weeks (restricted to non-squamous histology) or carboplatin (AUC 6) with a dose that will be capped to 700 mg and paclitaxel (90 mg/m²) D1 D8 D15 over 4 to 6 hours every 4 weeks, with a maximum of 4 cycles of carboplatin based doublet, and the possibility to use maintenance with pemetrexed.Type: DrugChemotherapy
Description: according to RECIST 1.1
Measure: Objective response rate Time: 2 yearsDescription: according to CTCAE version 4.0
Measure: Safety Time: 2 yearsDescription: according to CTCAE version 4.0
Measure: Tolerability Time: 2 yearsDescription: according to EQ-5D questionnaire
Measure: Quality of life Time: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years maximumDescription: according to EORTC QLQ-ELD14 questionnaire
Measure: Quality of life Time: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years maximumDescription: testing by immunochemistry
Measure: PD-L1 Time: 2 yearsDescription: according to geriatric mini data set
Measure: Geriatric evaluation Time: inclusion and 2 monthsAllocation: Randomized
Parallel Assignment
There are 2 SNPs
- Known activating mutation of EGFR (del LREA exon 19, mutation L858R or L861X of exon 21, mutation G719A/S in exon 18) or EML4-ALK or ROS-1 translocation - Superior at caval syndrome - Uncontrolled infectious status - All concurrent radiotherapy - Concurrent administration of one or several other anti-tumor therapies. --- L858R --- --- G719A ---
- Known activating mutation of EGFR (del LREA exon 19, mutation L858R or L861X of exon 21, mutation G719A/S in exon 18) or EML4-ALK or ROS-1 translocation - Superior at caval syndrome - Uncontrolled infectious status - All concurrent radiotherapy - Concurrent administration of one or several other anti-tumor therapies. --- L858R ---