Real-World Treatment Outcomes After Nivolumab Progression in BRAF-Negative Metastatic Melanoma: A Multicenter Cohort Study by the Turkish Oncology Group

Eniseler, Emine Bihter; Erdogan, Atike Pinar; Şahbazlar, Mustafa; Keskin Uzundere, Fatma; Şakalar, Teoman; Gür, Hasibe Bilge; Hacıbekiroğlu, İlhan; Balcık, Onur Yazdan; Beypınar, İsmail; Savsar, Mehmet Gürdal; Pempe, Gözde; Oksuz, Sila; Başoğlu, Tuğba; Demirkıran, Özge; Demir, Bilgin; Açıkgöz Yıldız, Bedriye; Demiray, Atike Gökçen; Akarca, Mehmet Sinan; Ünek, İlkay Tuğba; Kara, Mahmut; Urun, Muslih; Gökay, Ahmet Cebeli; Yeşil, Havva; Ekinci, Ferhat

doi:10.3390/jcm15135224

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Real-World Treatment Outcomes After Nivolumab Progression in BRAF-Negative Metastatic Melanoma: A Multicenter Cohort Study by the Turkish Oncology Group

by

Emine Bihter Eniseler

^1,*

,

Atike Pinar Erdogan

¹

,

Mustafa Şahbazlar

¹,

Fatma Keskin Uzundere

²

,

Teoman Şakalar

³,

Hasibe Bilge Gür

⁴

,

İlhan Hacıbekiroğlu

⁴,

Onur Yazdan Balcık

⁵,

İsmail Beypınar

⁵

,

Mehmet Gürdal Savsar

⁶,

Gözde Pempe

⁶,

Sila Oksuz

⁷

,

Tuğba Başoğlu

⁷

,

Özge Demirkıran

⁸,

Bilgin Demir

⁸

,

Bedriye Açıkgöz Yıldız

⁹

,

Atike Gökçen Demiray

⁹,

Mehmet Sinan Akarca

¹⁰

,

İlkay Tuğba Ünek

¹⁰

,

Mahmut Kara

¹¹

,

Muslih Urun

¹¹,

Ahmet Cebeli Gökay

¹²,

Havva Yeşil

¹²

and

Ferhat Ekinci

^1,*

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¹

Department of Medical Oncology, Manisa Celal Bayar University, Manisa 45030, Turkey

²

Department of Medical Oncology, Dicle University, Diyarbakir 21280, Turkey

³

Department of Medical Oncology, Kahramanmaraş Sütçü İmam University, Kahramanmaraş 46050, Turkey

⁴

Department of Medical Oncology, Sakarya University, Adapazari 54100, Turkey

⁵

Department of Medical Oncology, Alanya Alaaddin Keykubat Üniversitesi, Alanya 07425, Turkey

⁶

Department of Medical Oncology, Mersin Training and Research Hospital, Mersin 33000, Turkey

⁷

Department of Medical Oncology, Dr. Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi, Istanbul 34865, Turkey

⁸

Department of Medical Oncology, Aydin Adnan Menderes University, Aydin 09100, Turkey

⁹

Depatment of Medical Oncology, Pamukkale University, Denizli 20160, Turkey

¹⁰

Department of Medical Oncology, Dokuz Eylül University, Izmir 35330, Turkey

¹¹

Department of Medical Oncology, Van Yuzuncu Yil University, Van 65090, Turkey

¹²

Department of Medical Oncology, Gaziantep University, Gaziantep 27310, Turkey

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Authors to whom correspondence should be addressed.

J. Clin. Med. 2026, 15(13), 5224; https://doi.org/10.3390/jcm15135224

Submission received: 1 June 2026 / Revised: 30 June 2026 / Accepted: 1 July 2026 / Published: 3 July 2026

(This article belongs to the Section Oncology)

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Abstract

Background/Objectives: Despite improved survival with immune checkpoint inhibitors, the optimal treatment after anti-PD-1 progression in metastatic melanoma remains unclear. This study compared survival outcomes and treatment responses between chemotherapy (CT)- and immunotherapy (IO)-based therapies administered after nivolumab progression in patients with BRAF-negative metastatic melanoma. Methods: This multicenter retrospective study included patients with BRAF-negative metastatic melanoma who developed disease progression during nivolumab treatment. Post-progression systemic therapies were categorized as CT- or IO-based treatments. Treatment responses were assessed according to RECIST version 1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: A total of 141 patients were included. Following nivolumab progression, 107 (75.9%) received CT and 34 (24.1%) received IO. Based on best response to nivolumab, the objective response rate (ORR; CR + PR) was 55.1% in the CT group and 44.1% in the IO group. After post-nivolumab treatment, ORRs were 29.9% and 32.4% in the CT and IO groups, respectively, whereas complete response rates were higher with IO (21.2% vs. 3.0%). Median PFS was 4.17 months in the CT group and 3.9 months in the IO group (p = 0.403). Median OS was 7.83 and 8.17 months, respectively (p = 0.416). Elevated LDH level was identified as an independent adverse prognostic factor. Conclusions: In this multicenter real-world cohort, no statistically significant differences in survival were observed between patients receiving CT or IO after nivolumab progression. Given the retrospective, non-randomized study design, these findings should not be interpreted as evidence of comparative treatment efficacy. The higher CR rate observed with IO should be interpreted cautiously due to potential selection bias. Prospective studies are warranted to define the optimal treatment strategy after anti-PD-1 failure.

Keywords: metastatic melanoma; nivolumab; immune checkpoint inhibitors; chemotherapy; anti-PD-1 progression

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MDPI and ACS Style

Eniseler, E.B.; Erdogan, A.P.; Şahbazlar, M.; Keskin Uzundere, F.; Şakalar, T.; Gür, H.B.; Hacıbekiroğlu, İ.; Balcık, O.Y.; Beypınar, İ.; Savsar, M.G.; et al. Real-World Treatment Outcomes After Nivolumab Progression in BRAF-Negative Metastatic Melanoma: A Multicenter Cohort Study by the Turkish Oncology Group. J. Clin. Med. 2026, 15, 5224. https://doi.org/10.3390/jcm15135224

AMA Style

Eniseler EB, Erdogan AP, Şahbazlar M, Keskin Uzundere F, Şakalar T, Gür HB, Hacıbekiroğlu İ, Balcık OY, Beypınar İ, Savsar MG, et al. Real-World Treatment Outcomes After Nivolumab Progression in BRAF-Negative Metastatic Melanoma: A Multicenter Cohort Study by the Turkish Oncology Group. Journal of Clinical Medicine. 2026; 15(13):5224. https://doi.org/10.3390/jcm15135224

Chicago/Turabian Style

Eniseler, Emine Bihter, Atike Pinar Erdogan, Mustafa Şahbazlar, Fatma Keskin Uzundere, Teoman Şakalar, Hasibe Bilge Gür, İlhan Hacıbekiroğlu, Onur Yazdan Balcık, İsmail Beypınar, Mehmet Gürdal Savsar, and et al. 2026. "Real-World Treatment Outcomes After Nivolumab Progression in BRAF-Negative Metastatic Melanoma: A Multicenter Cohort Study by the Turkish Oncology Group" Journal of Clinical Medicine 15, no. 13: 5224. https://doi.org/10.3390/jcm15135224

APA Style

Eniseler, E. B., Erdogan, A. P., Şahbazlar, M., Keskin Uzundere, F., Şakalar, T., Gür, H. B., Hacıbekiroğlu, İ., Balcık, O. Y., Beypınar, İ., Savsar, M. G., Pempe, G., Oksuz, S., Başoğlu, T., Demirkıran, Ö., Demir, B., Açıkgöz Yıldız, B., Demiray, A. G., Akarca, M. S., Ünek, İ. T., ... Ekinci, F. (2026). Real-World Treatment Outcomes After Nivolumab Progression in BRAF-Negative Metastatic Melanoma: A Multicenter Cohort Study by the Turkish Oncology Group. Journal of Clinical Medicine, 15(13), 5224. https://doi.org/10.3390/jcm15135224

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Real-World Treatment Outcomes After Nivolumab Progression in BRAF-Negative Metastatic Melanoma: A Multicenter Cohort Study by the Turkish Oncology Group

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