Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial

Baize, Nathalie; Monnet, I.; Greillier, L.; Geier, M.; Léna, H.; Janicot, Henri; Vergnenègre, A.; Créquit, Jacky; Lamy, R.; Auliac, J.B.; Letreut, J.; Caer, H. Le; Gervais, Radj; Dansin, Éric; Madroszyk, Anne; Renault, P; Garff, G. Le; Falchero, L.; Bérard, H.; Schött, Roland; Saulnier, Patrick; Chouaïd, C.; investigators, Groupe Français de Pneumo-Cancérologie –

doi:10.1016/s1470-2045(20)30461-7

Cited by 90 publications

(85 citation statements)

References 24 publications

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“…68 A phase III RCT recently showed comparable outcomes in patients with sensitive relapse when treated with either topotecan or rechallenge with carboplatin plus etoposide. 69 Immunotherapy. The efficacy of nivolumab and pembrolizumab as third-line monotherapies in stage IV SCLC was assessed in small phase I/II studies.…”

Section: Standard Treatmentmentioning

confidence: 99%

Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆

et al. 2021

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Section: Standard Treatmentmentioning

confidence: 99%

Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆

et al. 2021

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“…2 Their median progression-free survival (mPFS) was only several months. [3][4][5] Amrubicin (AMR) is an anthracycline agent that was developed in Japan. In a phase 3 trial comparing AMR with topotecan in relapsed SCLC, AMR significantly improved overall response rate (ORR) and PFS and revealed similar overall survival (OS), despite failing to reveal superiority.…”

Section: Introductionmentioning

confidence: 99%

Pembrolizumab Plus Amrubicin in Patients With Relapsed SCLC: Multi-Institutional, Single-Arm Phase 2 Study

Akamatsu

Teraoka

Hayashi

et al. 2021

JTO Clinical and Research Reports

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Introduction In patients with relapsed SCLC, amrubicin (AMR) is the current standard treatment in Japan. Nevertheless, its efficacy is not satisfactory and prognosis is poor. Preclinical study suggested that anthracycline agent might induce immunogenic cell death and work synergistically with immune checkpoint inhibitors. Methods Patients with relapsed SCLC who relapsed after completion of platinum-containing regimen were registered. Patients were treated with pembrolizumab (200 mg, flat dose on d 1, every 3 wk for 2 y) plus AMR (40 mg/m 2 on d 1–3, every 3 wk until progression). Primary end point was overall response rate (ORR). Secondary end points consisted of progression-free survival (PFS), overall survival, and safety. On the basis of the hypothesis that this treatment will improve ORR from 20% to 40% (0.1 of one-sided α and power of 0.8), 25 patients are required (trial identifier: NCT03253068). Results Between November 2017 and October 2019, a total of 25 patients were enrolled. Most participants (88%) relapsed within 90 days after platinum-containing therapy and all patients were immune checkpoint inhibitor-naive. ORR, the primary end point, was 52.0% (95% confidence interval [CI]: 31.3%–72.2%). Median PFS was 4.0 months (95% CI: 2.8–7.0 mo), and PFS rate at 1 year was 14.4%. Median overall survival was 10.6 months (95% CI: 7.3–21.3 mo). Common adverse events greater than or equal to grade 3 were neutropenia (64%), leukopenia (40%), and febrile neutropenia (16%). No treatment-related deaths occurred. Conclusions Among patients with relapsed SCLC, pembrolizumab plus AMR was effective and tolerable.

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“…Even if combination regimens have more toxicity, the benefits are small and not durable. The rechallenge strategy with etoposide + platinum-based chemotherapy, however, at least in sensitive diseases, is a reasonable choice to have better response rates and progression-free survival with manageable toxicities ( 5 ). In this setting, the combination chemotherapy has shown high response rates (40-55%).…”

Section: Discussionmentioning

confidence: 99%

“…The primary toxicities of TOPO are hematologic, with most patients experiencing grade [G]3 or 4 neutropenia, anemia, or thrombocytopenia. Recently, a phase III study compared TOPO alone with a combination of carboplatin/etoposide as a rechallenge schedule in patients with sensitive relapsed SCLC ( 5 ). Although a combination did not increase median OS, it provided a two-month benefit in progression-free survival (PFS) and showed similar rates of severe (G3-4) hematological toxicities.…”

Section: Introductionmentioning

confidence: 99%

Topotecan or other agents as second‑line therapy for relapsed small‑cell lung cancer: A meta‑analysis of randomized studies

Petrelli¹,

Ghidini

Luciani³

2021

Mol Clin Oncol

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Small cell lung cancer (SCLC) is exceptionally responsive to chemotherapy and radiotherapy. In relapsed patients, particularly in resistant/refractory cases, the progression of disease occurs rapidly with second-line agents. Topotecan (TOPO), a camptothecin analog, is the only agent able to increase overall survival (OS) compared with the best supportive care alone. However, the efficacy of platinum-based chemotherapy rechallenge or other agents has not been systematically explored. In the present review, published articles, which evaluated outcome and toxicity associated with TOPO or non-TOPO-based chemotherapy in patients with SCLC from inception to September 2020 were systematically searched and identified by searching the PubMed, EMBASE and Cochrane Library databases. The primary outcome of interest was the risk of death (OS), and the secondary endpoints were risk of progression progression-free survival (PFS), overall response rate (ORR) and G3-4 hematological toxicities. A total of nine studies were included in quantitative synthesis for a total of 1,689 patients. They included platinum-based rechallenge, anthracycline-based combinations or camptothecin analogs. TOPO did not improve OS with respect to other therapies [hazard ratio (HR), 0.92; 95% confidence interval (95% CI), 0.78-1.09; P=0.33]. Similarly, PFS was similar in the two arms (HR, 1.1; 95% CI, 0.72-1.67; P=0.66). The ORR was not statistically higher with non-TOPO agents (relative risk, 1.53; 95% CI, 0.95-2.48). In subgroup analysis, combination chemotherapy was associated with an improved PFS but not OS or ORR compared with TOPO alone (HR, 1.85; 95% CI, 1.52-2.24; P<0.01). The rates of G3-4 anemia, febrile neutropenia and neutropenia were similar. In conclusion, in patients with relapsed SCLC, TOPO was associated with a similar survival, PFS and ORR as other agents. However, polychemotherapy was associated with improved PFS.

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Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial

Cited by 90 publications

References 24 publications

Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆

Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆

Pembrolizumab Plus Amrubicin in Patients With Relapsed SCLC: Multi-Institutional, Single-Arm Phase 2 Study

Topotecan or other agents as second‑line therapy for relapsed small‑cell lung cancer: A meta‑analysis of randomized studies

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