The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Oncol.
Sec. Skin Cancer
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1395378
Triple combination of vemurafenib, cobimetinib and atezolizumab in real clinical practice in Russian Federation: results of the A1 cohort of the ISABELLA study
Provisionally accepted- 1 Russian Cancer Research Center NN Blokhin, Moscow, Russia
- 2 The Russian Melanoma Professional Association (Melanoma.PRO), Moscow, Russia
- 3 Independent researcher, Moscow, Russia
- 4 St. Petersburg City Clinical Oncology Dispensary, St. Petersburg, Saint Petersburg, Russia
- 5 Hadassah Clinic, Moscow, Russia
- 6 Moscow Regional Clinical Oncological Dispensary, Balashikha, Russia
- 7 Ufa Republican Clinical Oncological Dispensary of the Ministry of Health, Republic of Bashkortostan, Ufa, Russia
- 8 Leningrad Regional Clinical Oncological Dispensary, Saint Petersburg, Russia
- 9 European Medical Center (EMC), Moscow, Moscow Oblast, Russia
- 10 Moscow City Oncological Hospital No.62, Moscow, Russia
- 11 Orenburg Regional Clinical Oncological Dispensary, Orenburg, Russia
- 12 State Autonomous Healthcare Institution of the Tyumen Region “Multidisciplinary Clinical Medical Center “Medical City”., Tyumen, Russia
- 13 Tula Regional Clinical Oncological Dispensary, Tula, Russia
- 14 Kurgan Regional Oncology Center, Kurgan, Russia
- 15 Nizhny Novgorod Regional Clinical Oncology Center, Nizhny Novgorod, Nizhny Novgorod Oblast, Russia
- 16 Kogkbuz Center of Oncology and Medical Radiology, Kirov, Russia
- 17 Independent researcher, Tambov, Russia
- 18 Murmansk Regional Oncological Dispensary, Murmansk, Russia
- 19 Regional Clinical Oncology Dispensary, Ryazan, Russia
- 20 Volgograd Regional Clinical Oncological Dispensary, Volgograd, Russia
Background: A new treatment approach for BRAF-mutant metastatic melanoma, combining BRAF and MEK inhibitors with an anti-PDL1 antibody, is emerging in Russia. It remains unclear which patients benefit most from this combination versus drug sequencing. This study evaluated patient characteristics and outcomes with this triple combination across fourteen Russian regions, focusing on biomarkers (PDL1 expression). Methods: This prospective non-interventional study included patients with skin melanoma treated with vemurafenib, cobimetinib, and atezolizumab (triple combination) no longer than 12 weeks before consent. The primary endpoint was 24-month overall survival (OS). Secondary endpoints included objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and quality of life (QoL). Adverse events were also recorded. Results: Between March 2021 and May 2023, 59 patients were enrolled across 19 centers in 14 regions. Among them, 31 patients had CNS metastases, with 18 symptomatic. Most patients (68%) received the triple combination as first-line treatment. Median follow-up was 16.83 months. ORR was 55.1%, with median DoR of 12.95 months (95% CI 11.0 to 14.8 months), with a median of 20.3 months (95% CI 9.1 to 31.5 months) when triple therapy was administered in the first line treatment. Median PFS was 13.6 months, and 24-month PFS was 22%. Median OS was 15.8 months, with a 24-month OS of 45%. No unexpected adverse events were reported; 38% of patients experienced grade 3-4 adverse events, primarily skin and liver toxicity. In multivariate Cox regression model biomarkers of interest (LDH, PD-L) did not have statistically significant impact on PFS, OS or DoR probably due to high data missing rate. Conclusion: The triple combination proved effective and tolerable in real-world settings.
Keywords: Metastatic melanoma1, BRAF-mutant2, Triple combination, brain metastases4, atezolizumab5, vemurafenib6, cobimetinib7
Received: 03 Mar 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Samoylenko, Kolonotareva, Kogay, Zhukova, Utyashev, Ivannikov, Menshikov, Zinkevich, Orlova, Vakhabova, Volkonsky, Beliavea, Butkov, Karabina, Moskovkina, Moshkova, Plishkina, Sychev, Cheplukhova, Chernova, Yurchenkov, Babina, Savelov and Demidov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Igor Samoylenko, Russian Cancer Research Center NN Blokhin, Moscow, Russia
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.