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 ... -  《-》

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 ... -  《-》

Profiling Preexisting Antibodies in Patients Treated With Anti-PD-1 Therapy for Advanced Non-Small Cell Lung Cancer.

Toi Y ，Sugawara S ，Sugisaka J ，Ono H ，Kawashima Y ，Aiba T ，Kawana S ，Saito R ，Aso M ，Tsurumi K ，Suzuki K ，Shimizu H ，Domeki Y ，Terayama K ，Nakamura A ，Yamanda S ，Kimura Y ，Honda Y ... -  《-》

Clinical Association Between Immune-related Adverse Events and Treatment Efficacy in Patients With Non-small-cell Lung Cancer Treated With Nivolumab-Ipilimumab-based Therapy.

Nivolumab and ipilimumab combination therapy has been extensively explored for the treatment of advanced non-small-cell lung cancer (NSCLC) through the pivotal phase III trials CheckMate 227 and CheckMate 9LA. However, the relationship between immune-related adverse events (irAEs) and the effectiveness of nivolumab plus ipilimumab-based therapy in a real-world clinical setting remains uncertain. We performed a retrospective analysis of 28 patients with advanced or recurrent NSCLC who underwent treatment with nivolumab plus ipilimumab, with or without platinum-doublet chemotherapy, from February 2021 to January 2023. The primary objective was to elucidate the clinical association between irAEs and treatment efficacy associated with nivolumab plus ipilimumab-based therapy. Among the 28 patients, 22 (78.6%) experienced irAEs. The median progression-free survival (PFS) was significantly longer for patients with irAEs than for those without (p=0.0158), as was overall survival (OS) (p=0.000394). The severity of irAEs had no significant influence on PFS or OS. The objective response rate tended to be higher in patients with irAEs than in those without (50.0% versus 0.0%, respectively; p=0.0549). Multivariate analysis indicated that irAE occurrence was an independent factor for improved PFS (hazard ratio=0.2084, p=0.01383) and OS (hazard ratio=0.0857, p=0.001588). Interstitial lung disease was inferior to other irAE profiles for both PFS and OS. Patients with advanced NSCLC experiencing irAEs demonstrated superior clinical outcomes when treated with nivolumab plus ipilimumab-based therapy compared with those without irAEs. However, immune-related interstitial lung disease may be less linked with PFS and OS than other irAE profiles.

Ebi N ，Inoue H ，Igata F ，Okuma R ，Kinoshita E ，Kawabata T ，Tan I ，Osaki Y ，Ikeda T ，Nakao A ，Shundo Y ，Hamada N ，Fujita M ... -  《-》

Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab.

Patients treated with nivolumab often experience its unique adverse events, called immune-related adverse events (irAEs). Regarding the mechanisms of immune-checkpoint inhibitors (ICIs), the occurrence of irAEs may also reflect antitumor responses. Here, we report the clinical correlation between irAEs and efficacy in NSCLC patients treated with nivolumab. Between December 2015 and February 2017, 38 advanced NSCLC patients were treated in our institution. All the patients were enrolled in our single-institutional, prospective, observational cohort study (UMIN000024414). IrAEs were defined as having a potential immunological basis that required more frequent monitoring and potential intervention. We divided the patients into two groups (irAEs group or no-irAEs group) and evaluated the objective response rate (ORR) and progression-free survival (PFS). The median age of the patients was 68.5 years (range 49-86 years); male/female ratio was 28/10; squamous/non-squamous cell carcinoma cases were 10/28; performance status was 0-1/2/3, 7/26/5. Among the overall population, ORR was 23.7% and median PFS was 91days. At the data cutoff, 14 irAEs were observed. The most common irAE was interstitial pneumonia (n=5). Other irAEs were hypothyroidism (n=4), hyperthyroidism, hypopituitarism, liver dysfunction, rash, and elevated thyroid stimulating hormone levels (n=1, each). Patients with irAEs had significantly higher ORRs compared with no-irAE patients (63.6% versus 7.4%, p <0.01). Similarly, the PFS among irAE patients was longer (median: not reached [95% confidence interval {CI}: 91days to not applicable]) than no-irAE patients (median 49days [95% CI: 36-127days], hazard ratio [HR] 0.10 [95% CI: 0.02-0.37, p<0.001]). Landmark analysis of patients who achieved PFS ≥60days demonstrated similar tendencies, but this was not significant (HR 0.28 [95% CI: 0.04-1.46], p=0.13). There was a correlation between irAE and efficacy in NSCLC patients treated with nivolumab.

Sato K ，Akamatsu H ，Murakami E ，Sasaki S ，Kanai K ，Hayata A ，Tokudome N ，Akamatsu K ，Koh Y ，Ueda H ，Nakanishi M ，Yamamoto N ... -  《-》