Safety and antitumor activity of durvalumab monotherapy in patients with pretreated extensive disease small-cell lung cancer (ED-SCLC).

Goldman, Jonathan W.; Dowlati, Afshin; Antonia, Scott; Nemunaitis, John; Butler, Marcus O.; Segal, Neil H.; Smith, Pamela A.; Weiss, Jared; Zandberg, Dan P.; Xiao, Feng; Angra, Natasha; Abdullah, Shaad E.; Gadgeel, Shirish M.

doi:10.1200/jco.2018.36.15_suppl.8518

Cited by 41 publications

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“…Results from clinical studies investigating the role of anti-PD-1/PD-L1 drugs in secondor further-line setting were conflicting so far, particularly when used as single-agent. [31][32][33][34][35][36] In the recently reported Phase 3 CheckMate-331 trial of nivolumab, a human IgG4 monoclonal antibody against PD-1, 569 SCLC patients relapsed on or following platinum-based chemotherapy were randomised (1:1) to receive either nivolumab (N = 284) or standard second-line chemotherapy (topotecan or amrubicin, N = 285). 37 Results of this study showed that, after 7.0-7.6 months of median follow-up, nivolumab did not yield a significant survival improvement (primary endpoint) compared to the standard chemotherapy arm (7.5 months [95% CI 5.6-9.2] versus 8.4 months [95% CI 7.0-10.0], p = 0.11).…”

Section: Discussionmentioning

confidence: 99%

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

et al. 2020

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Background Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC. Methods In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months). Conclusions Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met. Clinical Trial registration Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762.

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Section: Discussionmentioning

confidence: 99%

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

et al. 2020

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“…Recently reported phase 1/2 studies of immuno-oncology agents included biomarker-unselected patients treated with at least one prior line of therapy, with ORRs ranging from 9.5% to 18.7% and landmark 1-year OS rates of 28% to 43%. 11,[19][20][21] Ideally, identifying subsets of patients more likely to benefit from treatment with nivolumab monotherapy remains an important research goal. Tumor PD-L1 expression is a biomarker for response to PD-1 inhibitors in patients with NSCLC 22 ; however, as measured by using the validated Dako PD-L1 IHC 28-8 pharmDx assay, it did not appear to predict response to nivolumab in the present third-or later-line therapy analysis of CheckMate 032 or in an interim analysis of the secondor later-line nonrandomized cohort of this study.…”

Section: Discussionmentioning

confidence: 99%

Third-Line Nivolumab Monotherapy in Recurrent SCLC: CheckMate 032

Ready

Farago

Braud

et al. 2019

Journal of Thoracic Oncology

248

178

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Introduction: For patients with recurrent SCLC, topotecan remains the only approved second-line treatment, and the outcomes are poor. CheckMate 032 is a phase 1/2, multicenter, open-label study of nivolumab or nivolumab plus ipilimumab in SCLC or other advanced/metastatic solid tumors previously treated with one or more platinum-based chemotherapies. We report results of third-or later-line nivolumab monotherapy treatment in SCLC.Methods: In this analysis, patients with limited-stage or extensive-stage SCLC and disease progression after two or more chemotherapy regimens received nivolumab monotherapy, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety.Results: Between December 4, 2013, and November 30, 2016, 109 patients began receiving third-or later-line nivolumab monotherapy. At a median follow-up of 28.3 months (from first dose to database lock), the objective response rate was 11.9% (95% confidence interval: 6.5-19.5) with a median duration of response of 17.9 months (range 3.0-42.1). At 6 months, 17.2% of patients were progression-free. The 12-month and 18-month overall survival rates were 28.3% and 20.0%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 11.9% of patients. Three patients (2.8%) discontinued because of treatment-related adverse events.Conclusions: Nivolumab monotherapy provided durable responses and was well tolerated as a third-or later-line treatment for recurrent SCLC. These results suggest that nivolumab monotherapy is an effective third-or later-line treatment for this patient population. Ó 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

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“…10 It was shown to be tolerable and clinically active in urothelial carcinoma (UC), hepatocellular carcinoma, head and neck squamous cell carcinoma, gastroesophageal cancer, and SCLC in a phase I/II, global, multicenter, open-label, firstin-human study (Study 1108; NCT01693562) and in a phase 3 trial of patients with stage III, locally advanced, unresectable NSCLC (PACIFIC; NCT02125461). 6,[11][12][13][14][15] It has since been approved in the United States for locally advanced or metastatic UC after platinum-based chemotherapy, and in the United States and European Union for unresectable stage III NSCLC that has not progressed following concurrent chemoradiotherapy; the European Union approval is restricted to patients with PD-L1 expression greater than or equal to 1%. 16,17 This report describes the safety and clinical activity of durvalumab in patients with NSCLC from the doseescalation and dose-expansion phases of Study 1108 (described here as the NSCLC 10 mg/kg-every-2-weeks cohort) ( Supplementary Fig.…”

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confidence: 99%

Clinical Activity, Tolerability, and Long-Term Follow-Up of Durvalumab in Patients With Advanced NSCLC

Antonia

Balmanoukian

Brahmer

et al. 2019

Journal of Thoracic Oncology

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Safety and antitumor activity of durvalumab monotherapy in patients with pretreated extensive disease small-cell lung cancer (ED-SCLC).

Cited by 41 publications

References 0 publications

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

Third-Line Nivolumab Monotherapy in Recurrent SCLC: CheckMate 032

Clinical Activity, Tolerability, and Long-Term Follow-Up of Durvalumab in Patients With Advanced NSCLC

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