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Treatment Sequencing and Clinical Outcomes in BRAF-Positive and BRAF-Negative Unresectable and Metastatic Melanoma Patients Treated with New Systemic Therapies in Routine Practice

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Abstract

Background

Although BRAF/MEK inhibitors are generally considered to be equally effective whether given before or after immunotherapy, no prospective trial has confirmed this hypothesis and contradictory data have been published in the melanoma field.

Objective

We aimed to investigate the outcomes of patients with metastatic melanoma depending on the first-line treatment.

Patients and Methods

In this ambidirectional cohort, single-center study, we included 253 consecutive melanoma patients treated in our institution with an anti-PD1 antibody or BRAF/MEK inhibitors, who started first-line treatment between December 2015 and March 2018. Kaplan–Meier estimator, log-rank test, and Cox proportional hazard model were used in this analysis.

Results

First-line median progression-free survival (PFS) for all patients was 5.7 months (m), 6.9 m on anti-PD-1 therapy and 5.6 m for combination targeted therapy. Patients with BRAF mutated melanoma had 6.0 m median PFS on immunotherapy. At a median follow-up of 23.2 m with 149 events, in BRAF wild-type patients treated with anti-PD1, median overall survival (OS) was 18.1 m. BRAF mutated patients treated with first-line BRAF/MEK inhibitors had 11.7 m median OS. High neutrophil to lymphocyte ratio, high LDH level, ECOG > 0, and the presence of brain metastases negatively impacted PFS and OS.

Conclusions

In BRAF mutated patients with normal LDH, first-line immunotherapy seems a more effective approach. We have demonstrated that although BRAF mutation is a negative prognostic factor in stage IV melanoma, the use of two different systemic treatment modalities allows achievement of comparable survival in BRAF mutated and BRAF wild-type patients.

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Author notes

  1. Anna M. Czarnecka and Paweł Teterycz equally contributed to the work.

Authors and Affiliations

  1. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute, Oncology Center, Roentgena 5, 02-78, Warsaw, Poland

    Anna M. Czarnecka, Paweł Teterycz, Anna Mariuk-Jarema, Iwona Lugowska, Pawel Rogala, Monika Dudzisz-Sledz, Tomasz Switaj & Piotr Rutkowski

  2. Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

    Anna M. Czarnecka

  3. Early Phase Clinical Trials Unit, Maria Sklodowska-Curie Institute, Oncology Center, Warsaw, Poland

    Iwona Lugowska

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Correspondence to Anna M. Czarnecka.

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Funding

Data analysis and manuscript preparation were supported with Maria Sklodowska-Curie Institute-Oncology Center statutory founding.

Conflict of interest

Anna M. Czarnecka, Tomasz Switaj, Monika Dudzisz-Sledz, Iwona Lugowska, Piotr Rutkowski, and Pawel Rogala received support for travel and payment for lectures and consulting fees or honorarium form BMS, MSD, Roche, and Novartis. Piotr Rutkowski received grants from BMS and Novartis; consulting honoraria from BMS, MSD, Roche and Novartis; travel support from Pierre Fabre and Orphan drugs; advisory board honoraria from Novartis, Amgen, Blueprint Medicines, Pierre Fabre, BMS and MSD; and payment for lectures from Pfizer and Eli Lilly. Paweł Teterycz and Anna Mariuk-Jarema declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Czarnecka, A.M., Teterycz, P., Mariuk-Jarema, A. et al. Treatment Sequencing and Clinical Outcomes in BRAF-Positive and BRAF-Negative Unresectable and Metastatic Melanoma Patients Treated with New Systemic Therapies in Routine Practice. Targ Oncol 14, 729–742 (2019). https://doi.org/10.1007/s11523-019-00688-8

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