Immunotherapy in lung cancer: a real life retrospective and descriptive study in the Centre Hospitalier Jolimont

Background Nivolumab and Pembrolizumab are two human IgG4 PD-1 immune-checkpoint-inhibitor antibodies. They disrupt PD-1-mediated signaling and may restore antitumor immunity. Both were initially given as second or third line of treatment in non small cell lung cancer (NSCLC). Pembrolizumab is now used as first line treatment in locally advanced or metastatic NSCLC. Our aim was to compare real-life practice in the Centre Hospitalier Jolimont with the phase III clinical trials published for Nivolumab in NSCLCi. Methods In this retrospective study, we identified from our pharmacy databank the patients treated for NSCLC with Nivolumab or Pembrolizumab in the hospitals of the Centre Hospitalier Jolimont (3 hospitals) between 01/01/2016 and 31/12/2018. For these patients, we analysed population characteristics, overall survival, duration of treatment, causes of cessation of treatment and adverse events. We compared our results to phase III clinical trials published for Nivolumabi. Results 132 patients were identified, including 100 treated with Nivolumab and 32 with Pembrolizumab, median age 66 years, 62% male, 70% non squamous NSCLC, 64% on stage IVB, 22% with brain metastasis. Unlike the phase III clinical trials, we included all ECOG stages. Death (20%) and progression (41%) were the most frequent causes of cessation of treatment. Regarding adverse reactions, 8% of the patients presented a grade 3 or 4 (versus 7 to 10% in phase 3 clinical trials); 10% temporary interrupted the treatment and 2% definitely stopped the treatment due to adverse reactions. Cutaneous and endocrine adverse reactions were the most frequent (16% and 14% respectively). For patients treated with Nivolumab, the duration of treatment was longer than in phase III studies published (where RECIST criteria where strictly applied) : median of 6 months (95% CI 3.0 - 9.0) for non squamous NSCLC versus 2.3 months (95% CI, 2.2 – 3.3) ; median of 7 months (95% CI, 0.0 – 14.3) for squamous-cell NSCLC versus 3.5 months (95% CI, 2.1 -4.9). Overall survival was non inferior : median of 15 months (95% CI, 4.5 – 25.5) versus 12.2 months (95% CI, 9.7 - 15.0) for non squamous NSCLC ; median of 11 months (95% CI, 5.8 – 16.2) versus 9.2 months (95% CI, 7.3 – 13.3) for squamous-cell NSCLC. Conclusion Despite the inclusion of all ECOG stages, the overall survival time and the incidences of grade 3 and 4 adverse reactions in our population were similar to phase III clinical trials on selected patients having an ECOG score of 0 to 1. Treatment was continued for a longer period of time than in phase III studies (where RECIST criteria are strictly applied), with non inferior results on overall survival. These data confirm the promising perspective of using these molecules as first line treatment, including in advanced stage diseases in patients with altered general conditions