Nivolumab is now a reference treatment for patients with advanced non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy. Little data are available on treatment approaches following discontinuation of nivolumab and on the interest of a second course of immunotherapy after nivolumab discontinuation. The aims of this study were to describe treatment pathways following nivolumab discontinuation and to describe survival following retreatment with immunotherapy. Materials and methods: The analysis includes all patients with NSCLC recorded in a national hospital database, starting nivolumab in 2015-2016. Nivolumab treatment was considered discontinued if ≥3 infusions were missed. Patients starting a second course of PD-1 inhibitor following nivolumab discontinuation were analysed according to the duration of their initial nivolumab treatment course. Results: 10,452 patients were included (71 % men; mean age: 63.8 ± 9.6 years; squamous histology: 44 %). Median nivolumab treatment duration was 2.8 months [IQR :1.4-6.9]. Median OS was 11.5 months [95 %CI: 11.1-11.9]; 5118 (53.4 %) patients received post nivolumab therapy lines: 1517 (29.6 %) of these received a second course of PD-1 inhibitor, either after a treatment-free interval (resumption: n = 1127) or after intervening chemotherapy (rechallenge: n = 390). Median OS after nivolumab discontinuation was 15.0 months [13.9-16.7] in the resumption group and 18.4 months [14.8-21.9] in the rechallenge group. Median OS was significantly longer in patients with an initial nivolumab treatment duration ≥3 months. Conclusion: In this real-world setting, outcome after retreatment with a PD-1 inhibitor following a first course of nivolumab was significantly better in patients with a longer duration of initial nivolumab treatment.

Objective: To describe long-term outcomes of patients treated with nivolumab for advanced non-small cell lung cancer (aNSCLC) in everyday clinical practice in France, with a focus on patients aged ⩾80 years, patients with renal impairment and patients with brain metastases. Methods: The study included all patients with aNSCLC recorded in the French national hospital database, starting nivolumab in 2015–2016 and followed until December 2018. Patients were stratified by age, the presence of renal impairment and brain metastasis, as documented in the hospital discharge summaries. Information was retrieved on demographics, comorbidities and treatment history at baseline. Time to discontinuation of nivolumab treatment and overall survival were estimated using Kaplan–Meier survival analysis. Results: Overall, 10,452 patients were included, of whom 514 were octogenarians, 479 had renal impairment and 1800 had brain metastases at baseline. Median duration of nivolumab treatment was 2.8 months in the overall population and in both the octogenarian and renally impaired subgroups, and 2.3 months in patients with brain metastases. Median overall survival in these patient groups was 11.7 months (95% confidence interval: 11.3–12.2), 11.7 months (11.3–12.1), 11.7 months (11.3–12.2) and 9.9 months (9.0–10.9) respectively. Three-year overall survival rates were 19.1% (18.1–20.2) in the overall population, 16.5% (11.6–23.4) in octogenarians, 15.9% (11.8–21.4) in patients with renal impairment and 21.7% (19.4–24.2) in those with brain metastases. Conclusion: This large nationwide retrospective real-life cohort provided narrow estimates of long-term overall survival, which reached 19% at 3 years, consistent with data from phase III trials of nivolumab. Survival rates were comparable in the three special populations of interest and the overall population.

Background Immune checkpoint inhibitors (ICIs) are increasingly used to treat several types of tumors. Impact of this emerging therapy on patients’ health-related quality of life (HRQoL) is usually collected in clinical trials through standard questionnaires. However, this might not fully reflect HRQoL of patients under real-world conditions. In parallel, users’ narratives from social media represent a potential new source of research concerning HRQoL. Objective The aim of this study is to assess and compare coverage of ICI-treated patients’ HRQoL domains and subdomains in standard questionnaires from clinical trials and in real-world setting from social media posts. Methods A retrospective study was carried out by collecting social media posts in French language written by internet users mentioning their experiences with ICIs between January 2011 and August 2018. Automatic and manual extractions were implemented to create a corpus where domains and subdomains of HRQoL were classified. These annotations were compared with domains covered by 2 standard HRQoL questionnaires, the EORTC QLQ-C30 and the FACT-G. Results We identified 150 users who described their own experience with ICI (89/150, 59.3%) or that of their relative (61/150, 40.7%), with 137 users (91.3%) reporting at least one HRQoL domain in their social media posts. A total of 8 domains and 42 subdomains of HRQoL were identified: Global health (1 subdomain; 115 patients), Symptoms (13; 76), Emotional state (10; 49), Role (7; 22), Physical activity (4; 13), Professional situation (3; 9), Cognitive state (2; 2), and Social state (2; 2). The QLQ-C30 showed a wider global coverage of social media HRQoL subdomains than the FACT-G, 45% (19/42) and 29% (12/42), respectively. For both QLQ-C30 and FACT-G questionnaires, coverage rates were particularly suboptimal for Symptoms (68/123, 55.3% and 72/123, 58.5%, respectively), Emotional state (7/49, 14% and 24/49, 49%, respectively), and Role (17/22, 77% and 15/22, 68%, respectively). Conclusions Many patients with cancer are using social media to share their experiences with immunotherapy. Collecting and analyzing their spontaneous narratives are helpful to capture and understand their HRQoL in real-world setting. New measures of HRQoL are needed to provide more in-depth evaluation of Symptoms, Emotional state, and Role among patients with cancer treated with immunotherapy.

Background: The pharmacodynamic immune response to anti-PD-1 immunotherapy can be tracked in the peripheral blood of cancer patients and is associated with response to therapy. However, it is unclear how chemotherapy and chemoimmunotherapy affect T cell activity. Given the established role of these treatments in Non-Small Cell Lung Cancer (NSCLC), we sought to compare the impact of chemotherapy, chemoimmunotherapy, and immunotherapy on T cell immunity. Method: We prospectively collected blood samples in pts beginning chemotherapy, chemoimmunotherapy, or immunotherapy for metastatic NSCLC at baseline and with each cycle. Peripheral blood mononuclear cells were stained for immune markers and analyzed using 26 parameter flow cytometry. Immune response was characterized by increased expression of Ki67 on PD-1 expressing CD8 T cells. Statistical analysis was performed using paired t-test or Wilcoxon matched pairs analysis based on normality of data. All patients had CT scans with full RECIST 1.1 and tumor volume measurements. Result: We analyzed 28 pts (63% female, median age ¼ 65.5). 9 pts received chemotherapy, 12 pts immunotherapy, and 7 pts chemoimmunotherapy. Both immunotherapy (p ¼ 0.001) and chemoimmunotherapy (p¼0.016) resulted in an immune response that peaked at 3 weeks compared to baseline (Figure). No immune response was identified with chemotherapy (p¼0.734). Immune response was detected in exhausted T cells (PD1+CD39+ CD8) for both immunotherapy (p ¼0.007) and chemoimmunotherapy (p ¼0.031). In addition, chemoimmunotherapy induced activation of CD27+CCR7+ memory CD8 T cells (p¼0.0313), not seen with immunotherapy (p¼ 0.871).

Objectives Extrapolation is often required to inform cost-effectiveness (CE) evaluations of immune-checkpoint inhibitors (ICIs) since survival data from pivotal clinical trials are seldom complete. The objectives of this study were to evaluate the accuracy of estimates of long-term overall survival (OS) predicted in French CE assessment reports of ICIs, and to identify models presenting the best fit to the observed long-term survival data. Methods A systematic review of French assessment reports of ICIs in the metastatic setting since inception until May 2020 was performed. A targeted literature review was conducted to collect associated extended follow-up of randomized controlled trials (RCTs) used in the CE assessment reports. Difference between projected and observed OS was calculated. A range of standard parametric and spline-based models were applied to the extended follow-up data from the RCT to determine the best-fitting survival models. Results Of the 121 CE assessment reports published, 11 reports met the inclusion criteria. OS was underestimated in 73 percent of the CE assessment reports. The mean relative difference between each source was −13 percent (median: −15 percent; IQR: −0.4 to 26 percent). Models providing the best fit were those that could reflect nonmonotonic hazards. Conclusions Based on the available data at the time of submission, longer-term survival of ICIs was not fully captured by the extrapolation models used in CE assessments. Standard and flexible parametric models which can capture nonmonotonic hazard functions provided the best fit to the extended follow-up data. However, these models may still have performed poorly if fitted to survival data available at the time of submission to the French National Authority for Health.