Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non–Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis

Ksienski, Doran; Wai, Elaine S.; Croteau, Nicole; Fiorino, Leathia; Brooks, Edward G.; Poonja, Zia; Fenton, D.; Geller, G.; Glick, Daniel; Lesperance, Mary

doi:10.1016/j.cllc.2018.09.005

Cited by 75 publications

(66 citation statements)

References 21 publications

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“…When the relationship between the occurrence of nivolumab‐induced irAEs and nivolumab efficacy was analyzed by irAE category, the occurrence of rash, endocrine disorders, and gastrointestinal toxicity was correlated with the ORR to nivolumab. The occurrence of these three toxicities has previously been correlated with the efficacy of anti‐PD‐1 antibodies, and the present data appear to support these findings.…”

Section: Discussionsupporting

confidence: 88%

Three‐year follow‐up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non‐small cell lung cancer: Pooled analysis of ONO‐4538‐05 and ONO‐4538‐06 studies

Horinouchi¹,

Nishio

Hida

et al. 2019

Cancer Medicine

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Background Nivolumab is a programmed cell death 1 (PD‐1) receptor inhibitor antibody that enhances immune system antitumor activity. It is associated with longer overall survival (OS) than the standard treatment of docetaxel in patients with previously treated advanced squamous (SQ) and non‐squamous (non‐SQ) non‐small cell lung cancer (NSCLC). We previously conducted two phase II studies of nivolumab in Japanese patients with SQ (ONO‐4538‐05) and non‐SQ (ONO‐4538‐06) NSCLC, showing overall response rates (ORRs) (95% CI) of 25.7% (14.2‐42.1) and 22.4% (14.5‐32.9), respectively, with acceptable toxicity. In this analysis, we more precisely estimated the long‐term safety and efficacy in patients with SQ and non‐SQ NSCLC by pooling data from these two trials. Methods SQ (N = 35) and non‐SQ (N = 76) NSCLC patients received nivolumab (3 mg/kg, every 2 weeks) until progression or discontinuation. OS was estimated using the Kaplan–Meier method. A pooled analysis of SQ and non‐SQ patients was also performed. Results In SQ NSCLC patients, the median OS (95% CI) was 16.3 months (12.4‐25.2), and the estimated 1‐year, 2‐year, and 3‐year survival rates were 71.4% (53.4‐83.5), 37.1% (21.6‐52.7), and 20.0% (8.8‐34.4), respectively. In non‐SQ NSCLC patients, median OS was 17.1 months (13.3‐23.0), and the estimated 1‐, 2‐, and 3‐year survival rates were 68.0% (56.2‐77.3), 37.4% (26.5‐48.1), and 31.9% (21.7‐42.5), respectively. When SQ NSCLC and non‐SQ NSCLC data were pooled, the median OS was 17.1 months (14.2‐20.6), and the estimated 1‐, 2‐, and 3‐year survival rates were 69.1% (59.6‐76.8), 37.3% (28.3‐46.2), and 28.1% (20.0‐36.7), respectively. Twenty (76.9%) of 26 responders lived for 3 or more years. Nivolumab was well tolerated and no new safety signals were found. Conclusion Treatment with nivolumab improved long‐term survival and was well tolerated in patients with SQ and non‐SQ NSCLC. Trial registration JapicCTI‐132072; JapicCTI‐132073.

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Section: Discussionsupporting

confidence: 88%

Three‐year follow‐up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non‐small cell lung cancer: Pooled analysis of ONO‐4538‐05 and ONO‐4538‐06 studies

Horinouchi¹,

Nishio

Hida

et al. 2019

Cancer Medicine

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“…Cutaneous irAEs, rash and vitiligo in isolation, have been consistently associated with favorable outcomes, 8,9,13,16,17,20,23,24,26,27 except in one study in which the frequency was fairly low. 25 In our study, OS, PFS and ORR were consistently found to be superior in patients who experienced cutaneous irAEs or rash. Endocrine irAEs, all analyzed together or by taking into account single immune-related thyroid dysfunctions, have also been reported to be a favorable prognostic indicator, 9,11,20,22,24,26 with only one exception.…”

Section: Discussionsupporting

confidence: 61%

“…In patients with melanoma, 1-year OS and PFS were 49% [95%, CI 40-58] and 26% [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34], respectively (Supplementary Table 1). Median OS and PFS were 11.6 (iqr 3.4-29.6) and 3.9 (2.2-12.6) months, respectively.…”

Section: Efficacymentioning

confidence: 99%

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The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non–small-cell lung cancer: a real-life retrospective study

et al. 2019

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Background: Nivolumab and pembrolizumab, two PD1 inhibitors, trigger immune-related adverse events in approximately 50% of patients. Our objective was to determine whether these immunerelated adverse events are associated with patient outcomes. Patients and Methods: Retrospective cohort study, realized at the Institut Universitaire du Cancer de Toulouse, of all the patients treated with nivolumab or pembrolizumab off clinical trials. We included patients (i) diagnosed with unresectable stage III or stage IV melanoma or with recurrent stage IIIB or stage IV non-small cell lung cancer (ii) on nivolumab 3mg/kg or pembrolizumab 2mg/kg every 2 or 3 weeks respectively. Results: Of the 311 patients included (of 641 eligible subjects), 120 (38.6%) had melanoma and 191 (61.4%) had non-small cell lung cancer; 241 (77.5%) were treated with nivolumab with a median followup of 24 months (20-29). We observed 166 immune-related adverse events in 116 (37.3%) patients, categorized as "early" (onset before 12 weeks in melanoma and before 8 weeks in lung cancer) in 63 (54.3%) patients. Early and late adverse events were significantly associated with an increase in overall survival: adjusted hazard ratio 0.58 [0.41-0.84] (p = .003) and 0.28 [0.16-0.50] (p < .001) respectively. The overall response rate was significantly increased in patients with an immune-related adverse event (53.9% vs 12.9%, p < .001) Conclusions: This study validates the association between immune-related adverse events and anti-PD1 efficacy in real-life, especially if these events are delayed. Our results, along with further studies on the place of immunosuppressive drugs in the therapeutic strategy, could improve the management of these adverse events.

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“…Moreover, 12 out of 16 patients with GGO discontinued anti‐PD‐1 therapy after no more than 3 cycles. The relationship between the discontinuation of PD‐L1/PD‐1 therapy and poor outcome has been indicated previously . Early discontinuation of anti‐PD‐1 therapy could be correlated with worse prognosis in patients with GGO.…”

Section: Discussionmentioning

confidence: 88%

Prognostic significance of the radiologic features of pneumonitis induced by anti‐PD‐1 therapy

et al. 2020

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Background: Interstitial lung disease (ILD) induced by anti-programmed-cell death-1 (PD-1) and anti-PD-ligand 1 (PD-L1) is potentially life-threatening and is a common reason of the discontinuation of therapy. In contrast, an enhancement in antitumor effects was reported in patients who developed immune-related adverse events, including ILD. Although recent evidence suggests that radiologic patterns of ILD may reflect the severity of ILD and the antitumor immune responses to anti-PD-1/PD-L1 therapies, the association between radiologic features and clinical outcomes remains unclear. Methods: Patients with advanced non-small-cell lung cancer who were treated with 1st to 3rd line anti-PD-1 therapy from January 2016 through October 2017 were identified at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. ILD was diagnosed by the treating physicians, and chest computed tomography scans were independently reviewed to assess the radiologic features of ILD. Results: A total of 231 patients who received anti-PD-1 therapy were enrolled.Thirty-one patients (14%) developed ILD. Sixteen patients were classified as having ground glass opacities (GGO), 16 were classified as having cryptogenic organizing pneumonia (COP), and one was classified as having pneumonitis not otherwise specified. Patients with GGO had significantly worse overall survival time compared to patients with COP (7.8 months (95% CI: 2.2-NE) versus not reached (95% CI: 13.2-NE); P = 0.0175). Multivariate analysis of all 231 patients also revealed that PS = 1 and ≥2 and GGO were significant predictors of a worse overall survival.

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Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non–Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis

Cited by 75 publications

References 21 publications

Three‐year follow‐up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non‐small cell lung cancer: Pooled analysis of ONO‐4538‐05 and ONO‐4538‐06 studies

Three‐year follow‐up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non‐small cell lung cancer: Pooled analysis of ONO‐4538‐05 and ONO‐4538‐06 studies

The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non–small-cell lung cancer: a real-life retrospective study

Prognostic significance of the radiologic features of pneumonitis induced by anti‐PD‐1 therapy

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