Nivolumab and brain metastases in patients with advanced non-squamous non-small cell lung cancer

Crinò, Lucio; Bronte, Giuseppe; Bidoli, Paolo; Cravero, Paola; Minenza, Elisa; Cortesi, Enrico; Garassino, Marina Chiara; Proto, Claudia; Cappuzzo, Federico; Grossi, Francesco; Tonini, Giuseppe; Sarobba, Maria Giuseppina; Pinotti, Graziella; Numico, Gianmauro; Samaritani, Riccardo; Ciuffreda, Libero; Frassoldati, Antonio; Bregni, Marco; Santo, Antonio; Piantedosi, Francovito; Illiano, A; Marinis, Filippo de; Tamberi, Stefano; Giannarelli, Diana; Delmonte, Angelo

doi:10.1016/j.lungcan.2018.12.025

Cited by 116 publications

(75 citation statements)

References 22 publications

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“…Despite broader inclusion criteria used in EVIDENS, these effectiveness results are in line with those of the CheckMate 017 7 and 057 6 phase III trials and other real-world studies of nivolumab conducted in Europe ( Table 5). [15][16][17][18][19][20][21][22][23][24][25][26][27] Examination of the influence of baseline characteristics on OS did not reveal any significant effect of PD-L1 expression, although the analysis may have been underpowered to detect an association given that the sample size of patients in whom PD-L1 expression data were available was small. ECOG PS, smoking status, corticosteroids at baseline, EGFR mutation status, symptomatic brain metastasis and TRAEs significantly influenced OS in nivolumab recipients as seen in our multivariate analysis, even though some of these factors are also well-known prognostic factors in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…13 Instead, data have been reported from small patient cohorts, retrospective studies and early access programs, for which inclusion/exclusion enrollment criteria may be restrictive. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Due to known variation in cancer survival rates across Europe, 28 country-specific data may be more appropriate to describe the real-world experience with nivolumab in the treatment of NSCLC. Furthermore, data collected in the context of a real-world study can also help to address important clinical evidence gaps such as the outcomes in patients who were underrepresented in, or excluded from, pivotal clinical trials of nivolumab due to more severe comorbidities or poor prognostic factors.…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: preliminary results from the real-world EVIDENS study

et al. 2020

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EVIDENS is an ongoing, prospective, non-interventional study evaluating the effectiveness and safety of nivolumab in lung cancer patients in France (ClinicalTrials.gov NCT03382496).Adults with a pathologically confirmed diagnosis of lung cancer and initiating treatment with nivolumab were recruited from 146 sites in France. This analysis included only patients with non-small cell lung cancer (NSCLC) who received ≥1 nivolumab infusion, and evaluated patient characteristics at the time of nivolumab initiation and its effectiveness and safety after a median follow-up of 18 months.A total of 1,420 patients with NSCLC were included, most of whom had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (82.9%), non-squamous histology (69.2%) and stage IV disease (91.4%). Brain metastases were present in 19.9% of patients. Nivolumab was a secondline or ≥third-line regimen in 73.6% and 26.1% of patients, respectively. Almost all patients had prior chemotherapy (99.7%). Median overall survival was 11.2 months (95% confidence interval [CI]: 10.0--12.4). ECOG PS, smoking status, corticosteroids at baseline, epidermal growth factor receptor mutation status, presence of symptomatic brain metastases and treatment-related adverse events (TRAEs) were independent predictors of survival. Grade 3 and 4 TRAEs were reported in 105 (7.4%) and 12 (0.8%) patients, respectively; no treatment-related deaths were reported.Preliminary results of the EVIDENS study confirm the effectiveness and safety of nivolumab, mostly in pre-treated advanced NSCLC patients, with similar benefits to those observed in the phase III randomized clinical trials, despite a broader study population. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: preliminary results from the real-world EVIDENS study

et al. 2020

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“…In lung cancer, it is licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. Two large randomised studies in patients with advanced non-squamous (NSq) NSCLC (CheckMate057 [3]) and squamous (Sq) NSCLC (CheckMate017 [4]) comparing nivolumab to docetaxel have demonstrated its efficacy at extending overall survival (OS) [5,6], and the interest of nivolumab in treating NSCLC has been confirmed in many subsequent studies in routine clinical practice [7][8][9][10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy rechallenge after nivolumab treatment in advanced non-small cell lung cancer in the real-world setting: A national data base analysis

Levra¹,

Cotté²,

Corre³

et al. 2020

Lung Cancer

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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.

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“…In a phase II study (NCT02320058), a 1-year OS of 82.8% was observed, in 94 patients with MBM (9% RT-pretreated) and receiving a nivolumab and ipilimumab combination treatment ( 9 ). An Expanded Access Program (EAP) trial, which evaluated nivolumab efficacy in NSCLC, a 1-year OS of 43% was found, in patients with brain metastases ( N = 409, 69% RT-treated) ( 67 ). A thorough analysis of individual patient-level data from these studies would provide more accurate quantitative estimates of a ICI-RT combination benefit.…”

Section: Discussionmentioning

confidence: 99%

Quantification of Scheduling Impact on Safety and Efficacy Outcomes of Brain Metastasis Radio- and Immuno-Therapies: A Systematic Review and Meta-Analysis

Voronova¹,

Sekacheva

Helmlinger³

et al. 2020

Front. Oncol.

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Objectives: The goal of this quantitative research was to evaluate the impact of various factors (e.g., scheduling or radiotherapy (RT) type) on outcomes for RT vs. RT in combination with immune checkpoint inhibitors (ICI), in the treatment of brain metastases, via a meta-analysis. Methods: Clinical studies with at least one ICI+RT treatment combination arm with brain metastasis patients were identified via a systematic literature search. Data on 1-year overall survival (OS), 1-year local control (LC) and radionecrosis rate (RNR) were extracted; for combination studies which included an RT monotherapy arm, odds ratios (OR) for the aforementioned endpoints were additionally calculated and analyzed. Mixed-effects meta-analysis models were tested to evaluate impact on outcome, for different factors such as combination treatment scheduling and the type of ICI or RT used. Results: 40 studies representing a total of 4,359 patients were identified. Higher 1-year OS was observed in ICI and RT combination vs. RT alone, with corresponding incidence rates of 59% [95% CI: 54-63%] vs. 32% [95% CI: 25-39%] ( P < 0.001). Concurrent ICI and RT treatment was associated with significantly higher 1-year OS vs. sequential combinations: 68% [95% CI: 60-75%] vs. 54% [95% CI: 47-61%]. No statistically significant differences were observed in 1-year LC and RNR, when comparing combinations vs. RT monotherapies, with 1-year LC rates of 68% [95% CI: 40-90%] vs. 72% [95% CI: 63-80%] ( P = 0.73) and RNR rates of 6% [95% CI: 2-13%] vs. 9% [95% CI: 5-14%] ( P = 0.37). Conclusions: A comprehensive, study-level meta-analysis of brain metastasis disease treatments suggest that combinations of RT and ICI result in higher OS, yet comparable neurotoxicity profiles vs. RT alone, with a superiority of concurrent vs. sequential combination regimens. A similar meta-analysis using patient-level data from past trials, as well as future prospective randomized trials would help confirming these findings.

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Nivolumab and brain metastases in patients with advanced non-squamous non-small cell lung cancer

Cited by 116 publications

References 22 publications

Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: preliminary results from the real-world EVIDENS study

Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: preliminary results from the real-world EVIDENS study

Immunotherapy rechallenge after nivolumab treatment in advanced non-small cell lung cancer in the real-world setting: A national data base analysis

Quantification of Scheduling Impact on Safety and Efficacy Outcomes of Brain Metastasis Radio- and Immuno-Therapies: A Systematic Review and Meta-Analysis

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