{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:33:23Z","timestamp":1786361603005,"version":"build-2736575974"},"reference-count":21,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>Background: Second-line treatment selection in relapsed extensive-stage small-cell lung cancer (ES-SCLC) is commonly guided by the platinum-free interval, but the optimal approach for patients progressing 3\u20136 months after first-line platinum-based therapy remains uncertain. We compared platinum-containing doublet chemotherapy with single-agent chemotherapy in this clinically ambiguous subgroup. Methods: This multicenter retrospective real-world cohort study included patients with ES-SCLC or recurrent metastatic SCLC after prior limited-stage disease who received first-line platinum-based chemotherapy, achieved disease control, and progressed within a platinum-free interval of 90\u2013180 days. Treatment allocation was at the discretion of the treating physician and was not randomized. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Because of the non-randomized design, the treatment effect was examined across multiple analytic approaches, including multivariable Cox regression, propensity score adjustment, and stabilized inverse probability of treatment weighting (IPTW). Results: Of 105 patients, 54 received single-agent chemotherapy and 51 received platinum-containing doublet therapy; 39 (37.1%) had received first-line atezolizumab. Baseline characteristics were imbalanced in favor of the doublet group, which had a longer platinum-free interval, fewer pleural metastases, and a higher rate of objective response to first-line therapy. ORR was higher with doublet therapy (31.4% vs. 11.1%, p = 0.016), as was DCR (62.7% vs. 33.3%, p = 0.003). Median PFS was 4.4 months (95% CI 3.4\u20135.8) with doublet therapy versus 3.1 months (95% CI 2.7\u20133.7) with single-agent chemotherapy (unadjusted HR 0.53, 95% CI 0.36\u20130.80; p = 0.002). Median OS was 6.5 months (95% CI 5.4\u20138.0) versus 5.4 months (95% CI 4.1\u20136.0), a difference that was not statistically significant (HR 0.68, 95% CI 0.46\u20131.01; p = 0.054). The PFS estimate favored doublet therapy in all sensitivity analyses but was attenuated with increasingly complete adjustment for treatment selection (multivariable HR 0.46, 95% CI 0.29\u20130.72; propensity-adjusted HR 0.58, 95% CI 0.38\u20130.88; IPTW HR 0.68, 95% CI 0.38\u20131.20, p = 0.184). No OS estimate reached statistical significance in any model. Grade \u2265 3 adverse events were similar between groups (66.7% vs. 64.8%, p = 0.842). Conclusions: In this non-randomized cohort of patients relapsing within a 90\u2013180-day platinum-free interval, platinum-containing doublet chemotherapy was associated with higher response rates and longer PFS, without an increase in severe toxicity, but no overall survival benefit was demonstrated. Because baseline prognostic factors consistently favored the doublet group and the PFS advantage was attenuated after propensity-based adjustment, these findings should be regarded as hypothesis-generating. They are nonetheless consistent with randomized data showing improved PFS but not OS with platinum rechallenge, and support platinum-containing rechallenge as a reasonable option in carefully selected patients rather than as a demonstrated survival-prolonging strategy.<\/jats:p>","DOI":"10.3390\/curroncol33080472","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:24:53Z","timestamp":1786353893000},"page":"472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Revisiting Platinum Sensitivity in Relapsed Small-Cell Lung Cancer: Outcomes of Platinum-Containing Doublet Chemotherapy in the 3\u20136 Month Relapse Window"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6388-0346","authenticated-orcid":false,"given":"\u0130brahim","family":"\u00c7il","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4587-0726","authenticated-orcid":false,"given":"Maral Martin","family":"M\u0131ldano\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2184-634X","authenticated-orcid":false,"given":"Yasin","family":"Kutlu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3562-5006","authenticated-orcid":false,"given":"Ali Kaan","family":"G\u00fcren","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, School of Medicine, Marmara University, Istanbul 34899, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0596-1559","authenticated-orcid":false,"given":"Murat","family":"Sar\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, School of Medicine, Marmara University, Istanbul 34899, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2360-3392","authenticated-orcid":false,"given":"\u0130lker Nihat","family":"\u00d6kten","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital, Istanbul 34722, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-7853","authenticated-orcid":false,"given":"Fatih","family":"Atalah","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital, Istanbul 34722, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7336-4647","authenticated-orcid":false,"given":"Tuba","family":"Bayda\u015f","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital, Istanbul 34722, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cevat \u0130lteri\u015f","family":"K\u0131k\u0131l\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, School of Medicine, Ko\u00e7 University, Istanbul 34010, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Tural","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, School of Medicine, Ko\u00e7 University, Istanbul 34010, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1782-7808","authenticated-orcid":false,"given":"Ayberk","family":"Bayramgil","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6zde","family":"Balkaya Aykut","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pembeg\u00fcl","family":"Yumu\u015ftutan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1300-8944","authenticated-orcid":false,"given":"Eda","family":"Er\u00e7in","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bekir","family":"Do\u011fan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Bak\u0131rk\u00f6y Dr. Sadi Konuk Training and Research Hospital, Istanbul 34147, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1466-3887","authenticated-orcid":false,"given":"Mesut","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Bak\u0131rk\u00f6y Dr. Sadi Konuk Training and Research Hospital, Istanbul 34147, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4223-4940","authenticated-orcid":false,"given":"\u00d6zg\u00fcr","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul Training and Research Hospital, Istanbul 34098, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5721-9550","authenticated-orcid":false,"given":"B\u00fcnyamin","family":"G\u00fcney","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul Training and Research Hospital, Istanbul 34098, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0602-4778","authenticated-orcid":false,"given":"Sercan","family":"Olcar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kartal Dr. L\u00fctfi K\u0131rdar City Hospital, Istanbul 34865, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5757-4705","authenticated-orcid":false,"given":"Hatice","family":"Odaba\u015f","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kartal Dr. L\u00fctfi K\u0131rdar City Hospital, Istanbul 34865, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0443-6966","authenticated-orcid":false,"given":"Ahmet","family":"Bilici","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0406-715X","authenticated-orcid":false,"given":"Melike","family":"\u00d6z\u00e7elik","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3692","DOI":"10.21037\/jtd-20-3034","article-title":"Real-World Treatment Patterns and Outcomes in Small-Cell Lung Cancer: A Systematic Literature Review","volume":"13","author":"Johal","year":"2021","journal-title":"J. Thorac. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41568-025-00803-0","article-title":"Challenges of Small Cell Lung Cancer Heterogeneity and Phenotypic Plasticity","volume":"25","author":"Simpson","year":"2025","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s12094-012-0960-6","article-title":"Comparison of Second-Line Treatment Outcomes Between Sensitive and Refractory Small Cell Lung Cancer Patients: A Retrospective Analysis","volume":"15","author":"Korkmaz","year":"2013","journal-title":"Clin. Transl. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1056\/NEJMoa1809064","article-title":"First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer","volume":"379","author":"Horn","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/S0140-6736(19)32222-6","article-title":"Durvalumab plus Platinum-Etoposide versus Platinum-Etoposide in First-Line Treatment of Extensive-Stage Small-Cell Lung Cancer (CASPIAN): A Randomised, Controlled, Open-Label, Phase 3 Trial","volume":"394","author":"Dvorkin","year":"2019","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.annonc.2021.03.207","article-title":"Small-Cell Lung Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"32","author":"Dingemans","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/14737140.2024.2438067","article-title":"Lurbinectedin Is an Effective Alternative to Platinum Rechallenge and May Restore Platinum Sensitivity in Patients with Sensitive Relapsed Small Cell Lung Cancer","volume":"25","author":"Subbiah","year":"2025","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.21873\/invivo.11727","article-title":"Efficacy of Second-Line Chemotherapy in Patients with Sensitive Relapsed Small-Cell Lung Cancer","volume":"33","author":"Wakuda","year":"2019","journal-title":"In Vivo"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1016\/S1470-2045(20)30461-7","article-title":"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","volume":"21","author":"Baize","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107887","DOI":"10.1016\/j.lungcan.2024.107887","article-title":"Second-Line Treatment Outcomes after First-Line Chemotherapy plus Immunotherapy in Extensive-Stage Small Cell Lung Cancer (ES-SCLC) Patients: A Large French Multicenter Study","volume":"194","author":"Ezzedine","year":"2024","journal-title":"Lung Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jtho.2023.09.1446","article-title":"Reconsidering the Cutoff Value for Sensitive and Refractory Relapses in Extensive-Stage SCLC in the Era of Immunotherapy","volume":"19","author":"Torasawa","year":"2024","journal-title":"J. Thorac. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.6004\/jnccn.2018.0079","article-title":"NCCN Guidelines Insights: Small Cell Lung Cancer, Version 2.2018","volume":"16","author":"Kalemkerian","year":"2018","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-020-00235-0","article-title":"Small-Cell Lung Cancer","volume":"7","author":"Rudin","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e223","DOI":"10.1016\/j.cllc.2015.04.006","article-title":"Outcomes of Platinum-Sensitive Small-Cell Lung Cancer Patients Treated with Platinum\/Etoposide Rechallenge: A Multi-Institutional Retrospective Analysis","volume":"16","author":"Genestreti","year":"2015","journal-title":"Clin. Lung Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s12032-018-1123-6","article-title":"Rechallenge Treatment with a Platinum-Based Regimen in Patients with Sensitive Relapsed Small-Cell Lung Cancer","volume":"35","author":"Naito","year":"2018","journal-title":"Med. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5441","DOI":"10.1200\/JCO.2006.06.5821","article-title":"Phase III Trial Comparing Supportive Care Alone with Supportive Care with Oral Topotecan in Patients with Relapsed Small-Cell Lung Cancer","volume":"24","author":"Ciuleanu","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S1470-2045(20)30068-1","article-title":"Lurbinectedin as Second-Line Treatment for Patients with Small-Cell Lung Cancer: A Single-Arm, Open-Label, Phase 2 Basket Trial","volume":"21","author":"Trigo","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1056\/NEJMoa2307980","article-title":"Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer","volume":"389","author":"Ahn","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1200\/JCO.22.02823","article-title":"Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study","volume":"41","author":"Champiat","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cheema, P.K., Perdrizet, K.A., Sangha, R.S., Breadner, D., Daaboul, N., Farley, S., Jao, K., Liu, G., Logan, B., and Melosky, B. (2026). Early Experience with Tarlatamab (T-Cell Engagers) for Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Canada: Lessons Learned and Implementation Strategies. Curr. Oncol., 33.","DOI":"10.3390\/curroncol33020084"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/cncr.29098","article-title":"Small Cell Lung Cancer: Where Do We Go from Here?","volume":"121","author":"Byers","year":"2015","journal-title":"Cancer"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/8\/472\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:06:17Z","timestamp":1786359977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/8\/472"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,8]]},"references-count":21,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["curroncol33080472"],"URL":"https:\/\/doi.org\/10.3390\/curroncol33080472","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,8]]}}}