Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab: The Italian NSCLC expanded access program.

The incidence of any and of severe-grade immune-related adverse events (irAEs) with second-line nivolumab monotherapy is 31-65 % and 2-5 % respectively. While potentially serious and even fatal, in the absence of an appropriate therapy, such events might be indicators of the activation of the immune system and, potentially, of efficacy. We collected the records of 1959 non-small-cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access program, and we registered the appearance of any and of severe grade irAEs. We retrospectively searched for correlations between toxicity and efficacy parameters by using Cox's regression analysis. Overall, 342 (17.8%) patients developed an irAE of any grade. We observed that patients developing irAE of any grade achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9-7.1] vs 3.0 [95% CI: 2.8-3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5-19.9] vs 9.4 [95% CI: 8.4-10.4], p < 0.00001) compared to patients who did not. At multivariate analysis the development of an irAE remained an independent indicator of nivolumab efficacy (HR 1.44 [95% CI: 1.22-1.71] p < 0.0001). This report, performed in Caucasian NSCLC patients, showed that the appearance of irAEs correlated with outcome.

Baldini E ，Lunghi A ，Cortesi E ，Turci D ，Signorelli D ，Stati V ，Melotti B ，Ricciuti B ，Frassoldati A ，Romano G ，Ceresoli GL ，Illiano A ，Verderame F ，Fasola G ，Ricevuto E ，Marchetti P ，Pinto C ，Cartenì G ，Scotti V ，Tibaldi C ，Fioretto L ，Giannarelli D ... -  《-》

Immunotherapy as second-line treatment and beyond for non-small cell lung cancer in a single center of China: Outcomes, toxicities, and clinical predictive factors from a real-world retrospective analysis.

Real-world evidence of second-line treatment and beyond with immune checkpoint inhibitors (ICIs) in Chinese patients is lacking. Here, we aimed to assess the efficacy, responses, and immune-related side effects of anti-PD-1 agents in real-life practice. We retrospectively analyzed consecutive patients who received nivolumab or pembrolizumab monotherapy at Peking Medical College Hospital. We collected baseline characteristics, evaluated treatment efficacy, and categorized immune-related adverse effects (irAEs). Predictive factors of treatment response were also determined. The study included 97 patients with a median age of 64 years. The majority of patients were male, with nonsquamous histological type and advanced stage tumor, and had a history of smoking. Most patients received ICIs as second-line therapy. Expression of PD-L1 was detected in 34.11% patients. Overall response rate (ORR) and disease control rate (DCR) were 16.49% and 60.82%, respectively. None of the patients achieved complete response (CR). The median PFS and OS were150 days and 537 days, respectively. The incidence of immune-related toxicities was similar to the one previously reported. Patients with driver gene mutations had shorter PFS than patients without, while patients who encountered irAE had relatively longer PFS. The real-world clinical outcome of ICIs in second- and further-line NSCLC therapy is promising. Several characteristics may have predictive value for efficacy. Occurrence of irAEs during treatment was acceptable and could be an independent positive predictive for PFS. SIGNIFICANT FINDINGS OF THE STUDY: Efficacy and safety profile of ICIs as second-line treatment or above for patients with NSCLC are promising in real world circumstances Incidence and median time to the occurrence of irAEs vary between organs WHAT THIS STUDY ADDS: Driver gene mutations are associated with lower progression-free survival Occurrence of irAEs is associated with higher progression-free survival.

Chen M ，Li Q ，Xu Y ，Zhao J ，Zhang L ，Wei L ，Zhong W ，Wang M ... -  《-》

Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis.

Ricciuti B ，Genova C ，De Giglio A ，Bassanelli M ，Dal Bello MG ，Metro G ，Brambilla M ，Baglivo S ，Grossi F ，Chiari R ... -  《-》

Occurrence and number of immune-related adverse events are independently associated with survival in advanced non-small-cell lung cancer treated by nivolumab.

It has been found that occurrence of immune-related adverse events (irAEs) is associated with outcome in the treatment of advanced non-small-cell lung cancer (NSCLC) with anti-programmed cell death (PD)-1 or anti-PDL1 agents. Independent correlation with survival was not consistently demonstrated and correlation with the number of toxicities was also not previously described. All patients treated with nivolumab for advanced NSCLC, in the second line setting, were retrospectively reviewed in a single-center from March 2015 to March 2017. Sixty-nine patients were identified. After a median follow-up of 13 months (95% CI: 10.8; 15.3), there were 46 tumor progressions and 37 deaths. The 6-month and one-year progression-free survival (PFS) and overall survival (OS) rates were 29%/61% and 24%/49%, respectively. Thirty-one patients (44.9%) presented irAEs. Patients presenting tumor response to previous chemotherapy had a higher rate of irAEs (P=0.01) and a better OS (HR=2, P=0.04). Occurrence of irAEs correlated with OS in multivariate analysis (HR=0.4, 95% CI [0.19; 0.8], P=0.02). The number of irAEs correlated with tumor response, PFS and OS in univariate analysis. Having≥2 irAEs correlated with better outcome compared with one irAE, which correlated with better tumor response and PFS in comparison with 0 irAE, in multivariate analysis. In this study, irAEs was associated with a better outcome in patients treated with nivolumab for advanced NSCLC in the second line setting. Interestingly, the number of irAEs correlated with tumor response and PFS.

Bouhlel L ，Doyen J ，Chamorey E ，Poudenx M ，Ilie M ，Gal J ，Guigay J ，Benzaquen J ，Marquette CH ，Berthet JP ，Mouroux J ，Schiappa R ，Padovani B ，Hofman P ，Otto J ... -  《-》

Outcomes associated with immune-related adverse events in metastatic non-small cell lung cancer treated with nivolumab: a pooled exploratory analysis from a global cohort.

Naqash AR ，Ricciuti B ，Owen DH ，Florou V ，Toi Y ，Cherry C ，Hafiz M ，De Giglio A ，Muzaffar M ，Patel SH ，Sugawara S ，Burkart J ，Park W ，Chiari R ，Sugisaka J ，Otterson GA ，de Lima Lopes G ，Walker PR ... -  《-》