The Role of Immune-Related Adverse Events in Prognosis and Efficacy Prediction for Patients with Non-Small Cell Lung Cancer Treated with Immunotherapy: A Retrospective Clinical Analysis.

The development of immune-related adverse events (irAEs) in patients undergoing immunotherapy has been reported to be a favorable prognostic factor in several studies. We aimed to examine the correlation between irAEs and prognosis in patients with non-small cell lung cancer (NSCLC) and further reveal the patient characteristics associated with response to immunotherapy among treatment responders who developed irAEs. We retrospectively enrolled 80 patients with NSCLC who received immunotherapy at Shinshu University Hospital between February 2016 and February 2020. Progression-free survival (PFS) and overall survival (OS) were compared between patients with and those without irAEs. We examined the prognostic factors associated with PFS and OS using univariate and multivariate Cox proportional-hazards models. We further analyzed the patients who developed irAEs by classifying them into responders and non-responders. Twenty-five patients developed irAEs. The median PFS and OS of the patients with irAEs were significantly longer than those of the patients without irAEs (6.8 vs. 1.9 months, p < 0.001, and 37.8 vs. 8.1 months, p < 0.001, respectively). Multivariate analysis associated with PFS and OS indicated that the development of irAEs was an independent favorable prognostic factor. Among the patients developing irAEs, the responder group had a significantly higher incidence of multiple irAEs than the non-responder group (41.7 vs. 0.0%, p = 0.009). Our findings revealed that the development of irAEs was associated with clinical benefits in NSCLC patients who received immunotherapy. In particular, patients with multiple irAEs might have good prognoses.

Sonehara K ，Tateishi K ，Araki T ，Komatsu M ，Yamamoto H ，Koizumi T ，Hanaoka M ... -  《-》

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 ... -  《-》

Association Between Immune-related Adverse Events and Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer.

Immune checkpoint inhibitors (ICIs) are available for first- and further lines of treatment of patients with advanced non-small-cell lung cancer (NSCLC). These treatments are associated with adverse events called immune-related adverse events (IRAEs). The incidence, diagnosis, and treatment of IRAEs are quite acknowledged; however, the link between IRAEs and the efficacy of ICIs requires further clarification. The objectives of this study were to assess the association between IRAEs incidence and severity and ICIs efficacy in patients with advanced NSCLC. In this retrospective study, clinical, biological, treatment, and outcome data were collected from patients with advanced NSCLC who received at least 1 cycle of ICIs from April 2013 to February 2017. The primary endpoint was to assess the association of IRAEs incidence with overall survival (OS). Secondary endpoints were the association of IRAEs with progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Overall, 270 patients were studied. The median OS was 14 months, median PFS was 2.6 months, ORR was 13%, and DCR was 51%. OS, PFS, and ORR were significantly better for patients with IRAEs compared with patients with no IRAEs, translating to median OS not reached versus 8.21 months, respectively (hazard ratio, 0.29; 95% confidence interval [CI], 0.18-0.46; P < .001); PFS was 5.2 versus 1.97 months (hazard ratio, 0.42; 95% CI, 0.32-0.57; P < .001); and ORR was 212.9% versus 5.7% (odds ratio, 4.9; 95% CI, 2.18-11.05; P < .001). This report presents the largest case series showing longer OS and PFS and better ORR when IRAEs occurred in a population of patients with advanced NSCLC treated with ICIs. The biological background for this phenomenon is being explored prospectively.

Grangeon M ，Tomasini P ，Chaleat S ，Jeanson A ，Souquet-Bressand M ，Khobta N ，Bermudez J ，Trigui Y ，Greillier L ，Blanchon M ，Boucekine M ，Mascaux C ，Barlesi F ... -  《-》

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 ... -  《-》