Efficacy and Safety of Nivolumab in Previously Treated Patients With Non-Small-cell Lung Cancer: Real World Experience in Argentina.

Nivolumab was the first anti-programmed cell death 1 drug approved in Argentina for non-small-cell lung cancer treatment in the second-line setting. The present study was a multicenter, observational, retrospective study of patients with progression to stage IV NSCLC during platinum-based chemotherapy who had received nivolumab monotherapy in a drug-expanded access program in Argentina. The data from 109 patients were assessed retrospectively for safety and clinical outcomes. The follow-up period was 8.83 months (interquartile range, 3.4-12.67); 57.8% were men, 29.4% were current smokers, and 78.0% had a diagnosis of nonsquamous cell cancer. The median number of chemotherapy lines before nivolumab was 2 (range, 1-4). Also, 59.6% had received radiotherapy and 89% had received platinum-based chemotherapy. The drug-related toxicity rate was 78.9%, the grade 2-3 toxicity rate was 28.4%, and 33.9% of patients had required corticosteroids. The treatment response was evaluated in 104 patients. The best response was a complete response in 2 (2%), partial response in 28 (27%), stable disease in 33 (32%), and progressive disease in 41 (39%). Univariate analysis revealed that the absence of corticosteroid use (P = .034), toxicity grade 1-3 (P = .0025), and performance status of ≤ 1 (P = .049) were associated with longer disease-free survival, performance status of ≤ 1 (P < .001), and toxicity grade 1-3 (P = .001) were associated with longer overall survival. On multivariate Cox regression analysis, toxicity grade 1-3 (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24-0.81; P = .008) and age ≤ 50 years (HR, 0.28; 95% CI, 0.13-0.61; P = .001) were associated with longer progression-free survival and corticosteroid use was associated with shorter progression-free survival (HR, 2.06; 95% CI, 1.22-3.48; P = .007). The use of nivolumab in the real world setting in patients with heavily pretreated NSCLC was well tolerated and showed promising clinical efficacy. The performance status, use of corticosteroids, and immune-mediated toxicity seem to be the conditions that can affect the clinical outcomes.

Martin C ，Lupinacci L ，Perazzo F ，Bas C ，Carranza O ，Puparelli C ，Kowalyszyn R ，Magri I ，Varela M ，Richardet E ，Vera K ，Foglia S ，Jerez I ，Aman E ，Martinengo G ，Batagelj E ，Dri A ，Pilnik N ，Roa GM ，Mando P ，Tsou F ，Recondo G ，Cayol F ，Flores M ，Sena S ，Bagnes C ，Waisberg FD ，Minatta JN ，Rizzo M ... -  《-》

Real-world effectiveness and safety of nivolumab in patients with non-small cell lung cancer: A multicenter retrospective observational study in Japan.

To describe the treatment patterns and determine the effectiveness and safety of nivolumab treatment for non-small cell lung cancer (NSCLC) in real-world setting in Japan. Japanese patients with NSCLC who received nivolumab were analyzed retrospectively. Patients who had started nivolumab treatment between April 2016 and December 2016 were enrolled. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness and safety of nivolumab treatment and that of treatments just before and after nivolumab treatment, and programmed death-ligand 1 (PD-L1) expression status, if available, were collected. Factors associated with nivolumab effectiveness identified by univariate and multivariate analyses were further investigated for plotting Kaplan-Meier curves of epidermal growth factor receptor (EGFR) gene mutation status, PD-L1 expression status, and Eastern Cooperative Oncology Group performance status (ECOG PS). In this study, 901 NSCLC patients were enrolled. Nivolumab was used the most as a second line treatment with a median number of nivolumab doses of five. The median overall survival (OS) was 14.6 months, one-year survival rate was 54.3 %, and median progression-free survival (PFS) was 2.1 months. The objective response rate was 20.5 % and disease control rate was 57.4 %. According to multivariate analyses, better OS and PFS were associated with favorable ECOG PS and absence of liver metastasis. Better PFS was observed in patients without EGFR mutation and patients with smoking history. PFS and best overall response in PD-L1 expression subgroups were expression level-dependent. The overall incidence of irAEs was 45.8 %, and the incidence of adverse events of grade 3 or higher was 14.0 %. The real-world effectiveness and safety of nivolumab is consistent with that reported by previous clinical trials and other real-world data. Subgroup analysis showed that ECOG PS, EGFR mutation status, smoking status, and PD-L1 were associated with the effectiveness of nivolumab.

Morita R ，Okishio K ，Shimizu J ，Saito H ，Sakai H ，Kim YH ，Hataji O ，Yomota M ，Nishio M ，Aoe K ，Kanai O ，Kumagai T ，Kibata K ，Tsukamoto H ，Oizumi S ，Fujimoto D ，Tanaka H ，Mizuno K ，Masuda T ，Kozuki T ，Haku T ，Suzuki H ，Okamoto I ，Hoshiyama H ，Ueda J ，Ohe Y ... -  《-》

Pseudoprogression in Previously Treated Patients with Non-Small Cell Lung Cancer Who Received Nivolumab Monotherapy.

Nivolumab is effective in the treatment of previously treated patients with advanced NSCLC. However, its radiological evaluation is challenging because of atypical patterns of response such as pseudoprogression. We examined the characteristics and outcomes of previously treated patients with NSCLC who were treated with nivolumab and experienced development of pseudoprogression. We conducted a 15-center retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab monotherapy. For the patients who showed pseudoprogression, we defined progression-free survival 1 (PFS1) as the time to Response Evaluation Criteria in Solid Tumors-defined first progressive disease and progression-free survival 2 (PFS2) as the time to Response Evaluation Criteria in Solid Tumors-defined second progressive disease or death. Among the 542 patients included, 20% and 53% showed a typical response and progression, respectively. Of the 14 (3%) patients who showed pseudoprogression, most (n = 10) showed a response within 3 months of nivolumab treatment. The median PFS1 and PFS2 were 1.0 and 7.3 months, respectively. The median PFS2 was significantly shorter in the patients who showed pseudoprogression than the PFS of the patients with a typical response (p < 0.001). In contrast, patients showing pseudoprogression had significantly longer overall survival than did patients showing typical progression (p = 0.001). Pseudoprogression was uncommon, and the duration of response in patients who showed pseudoprogression was shorter than that in patients who showed a typical response. However, the survival benefit of pseudoprogression was markedly better than that of typical progression. Further research is required to elucidate the characteristics of and mechanisms underlying pseudoprogression.

Fujimoto D ，Yoshioka H ，Kataoka Y ，Morimoto T ，Hata T ，Kim YH ，Tomii K ，Ishida T ，Hirabayashi M ，Hara S ，Ishitoko M ，Fukuda Y ，Hwang MH ，Sakai N ，Fukui M ，Nakaji H ，Morita M ，Mio T ，Yasuda T ，Sugita T ，Hirai T ... -  《-》

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 ... -  《-》

Efficacy and Safety of Anti-PD-1 Immunotherapy in Patients Aged ≥ 75 Years With Non-small-cell Lung Cancer (NSCLC): An Italian, Multicenter, Retrospective Study.

Non-small-cell lung cancer (NSCLC) is predominantly a disease of the elderly population. Over the past few years, immunotherapy with monoclonal antibodies named checkpoint inhibitors (ICIs) greatly improved the clinical management of a significant proportion of patients with metastatic NSCLC. However, pivotal trials excluded older patients, although, given the favorable clinical profile of ICIs, this treatment may be revealed to be a most valuable option also for these patients. To this aim, a multicenter retrospective analysis was performed on patients aged ≥ 75 years with NSCLC treated with anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy. Inclusion criteria were: diagnosis of locally advanced or metastatic NSCLC (stage IIIB or IV, according to the American Joint Committee on Cancer (AJCC) classification system, version 8.0); age ≥ 75 years; treatment with anti-PD-1/PD-L1 monoclonal antibodies in first or subsequent lines of treatment; absence of epidermal growth factor receptor-activating mutations or anaplastic lymphoma kinase and ROS-1 rearrangements. The primary endpoints of the study were the efficacy, in terms of overall response rate, progression-free survival, and overall survival, and safety, by means of evaluations of the incidence of immune-related adverse events. Eighty-six patients were considered for the final analysis; 71 (82.6%) were male. The mean age was 78.5 years (range, 75-86 years; SD, 3.12 years). Of the 86 patients, 69 (80.2%) of patients had a performance status of 0 or 1. The overall median progression-free survival was 5.6 months (range 1-36 months; SD, 7.5 months,) whereas the median overall survival was 10.1 months (range, 1.7-34.8 months; SD, 8 months). At the Cox regression analysis, the only parameter significantly associated with survival was the smoking status (P = .008). No difference in survival was found between patients younger and older than 80 years. In the present real-world retrospective cohort, efficacy and toxicity profiles of ICIs in older patients with advanced NSCLC were comparable with those observed in younger patients enrolled in clinical trials.

Luciani A ，Marra A ，Toschi L ，Cortinovis D ，Fava S ，Filipazzi V ，Tuzi A ，Cerea G ，Rossi S ，Perfetti V ，Rossi A ，Giannetta L ，Sala L ，Finocchiaro G ，Pizzutilo EG ，Carelli S ，Agustoni F ，Cergnul M ，Zonato S ，Siena S ，Bidoli P ，Ferrari D ... -  《-》