Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 8/2019

01-08-2019 | Melanoma | Research Article

Efficacy of rechallenge with BRAF inhibition therapy in patients with advanced BRAFV600 mutant melanoma

Authors: D. Viñal, D. Martinez, E. Espinosa

Published in: Clinical and Translational Oncology | Issue 8/2019

Login to get access

Abstract

Background

The treatment of patients with BRAFv600 mutant melanomas progressing to BRAF inhibitors (BRAFi) and immunotherapy remains challenging. Preclinical studies and a small phase 2 trials have recently suggested that rechallenging with BRAFi may have a roll in these patients. The aim of this systematic review was to summarise the current evidence on the efficacy of BRAF inhibition therapy rechallenge after progression to BRAFi in metastatic BRAFv600 melanoma patients.

Materials and methods

We performed a systematic literature search in MEDLINE, Embase and the Cochrane Library CENTRAL up to November 2018. The target was restricted to patients with unresectable and/or metastatic BRAF V600 mutant melanoma that had previously progressed on BRAFi, were off-treatment for a period of time and then retreated with a BRAF inhibition strategy. We included prospective trials, observational studies and case reports. The primary outcomes were overall response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and median overall survival since the start of the treatment.

Results

Up to November 2018, nine reports met our inclusion criteria: five case reports, three observational studies and a phase 2 trial. No comparative studies have been reported. In total, 188 patients met the inclusion criteria for this review. Efficacy results of the observational reports and the clinical trial are presented. ORR varied between 28 and 43% and DCR between 57 and 72%. Duration of response was reported in 1 retrospective study and was of 14 months. PFS varied between 4.9 and 5 months and OS was not reported in all studies.

Conclusion

Although no comparative studies have been conducted, rechallenging with BRAF inhibition therapy seems a plausible treatment option. Randomized trials are needed to confirm these results.
Literature
1.
Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367:1694.CrossRefPubMedPubMedCentral
2.
Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371:1867.CrossRefPubMed
3.
Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19:603.CrossRefPubMed
4.
Koppolu V, Rekha Vasigala VK. Checkpoint immunotherapy by nivolumab for treatment of metastatic melanoma. J Cancer Res Ther. 2018;14(6):1167–75.PubMed
5.
Hauschild A, Agarwala SS, Trefzer U, Hogg D, Robert C, Hersey P, et al. Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol. 2009;27:2823.CrossRefPubMed
6.
Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, et al. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature. 2013;494(7436):251–5.CrossRefPubMedPubMedCentral
7.
Smith MP, Holly Brunton H, Rowling EJ, Ferguson J, Arozarena I, Miskolczi Z, et al. Inhibiting drivers of non-mutational drug tolerance is a salvage strategy for targeted melanoma therapy. Cancer Cell. 2016;29:270–80.CrossRefPubMedPubMedCentral
8.
Schreuer M, Jansen Y, Planken S, Chevolet I, Seremet T, Kruse V, et al. Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAF V600-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial. Lancet Oncol. 2017;18:464–72.CrossRefPubMed
9.
Desvignes C, Abi Rached H, Templier C, Drumez E, Lepesant P, Desmedt E, et al. BRAF inhibitor discontinuation and rechallenge in advanced melanoma patients with a complete initial treatment response. Melanoma Res. 2017;27(3):281–7.CrossRefPubMed
10.
Seghersa AC, Wilgenhof S, Lebbé C, Neyns B. Successful rechallenge in two patients with BRAF-V600-mutant melanoma who experienced previous progression during treatment with a selective BRAF inhibitor. Melanoma Res. 2012;22:466–72.CrossRef
11.
Romano E, Pradervand S, Paillusson A, Weber J, Harshman K, Muehlethaler K, et al. Identification of multiple mechanisms of resistance to Vemurafenib in a patient with BRAFV600E-mutated cutaneous melanoma successfully rechallenged after progression. Clin Cancer Res. 2013;19(20):5749–57.CrossRefPubMed
12.
Mackiewicz-Wysocka M, Krokowicz L, Kocur J, Mackiewicz J. Resistance to Vemurafenib can be reversible after treatment interruption a case report of a metastatic melanoma patient. Medicine (Baltimore). 2014;93(27):e157.CrossRef
13.
Roux J, Pages C, Malouf D, Basset Seguin N, Madjlessi N, Baccard M, et al. BRAF inhibitor rechallenge in patients with advanced BRAF V600-mutant melanoma. Melanoma Res. 2015;25:559–63.CrossRefPubMed
14.
Rogiers A, Wolter P, Bechter O. Dabrafenib plus trametinib rechallenge in four melanoma patients who previously progressed on this combination. Melanoma Res. 2017;27:164–7.CrossRefPubMed
15.
Amann VC, Hoffmann D, Mangana J, Dummer R, Goldinger SM, et al. Successful retreatment with combined BRAF/MEK inhibition in metastatic BRAFV600-mutated melanoma. JEADV. 2017;31:1638–40.PubMed
16.
Valpione S, Carlino MS, Mangana J, Mooradian MJ, McArthur G, Schadendorf D, et al. Rechallenge with BRAF-directed treatment in metastatic melanoma: a multi-institutional retrospective study. Eur J Cancer. 2018;91:116–24.CrossRefPubMed
17.
Tietze JK, Forschner A, Loquai C, Mitzel-Rink H, Zimmer L, Meiss F, et al. The efficacy of re-challenge with BRAF inhibitors after previous progression to BRAF inhibitors in melanoma: a retrospective multicenter study. Oncotarget. 2018;9(76):34336–46.CrossRefPubMedPubMedCentral
18.
Middleton MR, Grob JJ, Aaronson N, Hogg D, Robert C, Hersey P, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000;18:158.CrossRefPubMed
19.
Avril MF, Aamdal S, Grob JJ, Hauschild A, Mohr P, Bonerandi JJ, et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol. 2004;22:1118.CrossRefPubMed
20.
Flaherty KT, Lee SJ, Zhao F, Schuchter LM, Flaherty L, Kefford R, et al. Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma. J Clin Oncol. 2013;31:373.CrossRefPubMed
21.
Sun C, Wang L, Huang S, Heynen GJ, Prahallad A, Robert C, et al. Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma. Nature. 2014;508:118–22.CrossRef
22.
Cappuzzo F, Morabito A, Normanno N, Bidoli P, Del Conte A, Giannetta L, et al. Efficacy and safety of rechallenge treatment with gefitinib in patients with advanced non-small cell lung cancer. Lung Cancer. 2016;99:31–7.CrossRefPubMed
23.
Italiano A, Cioffi A, Coco P, Maki RG, Schöffski P, Rutkowski P, et al. Patterns of care, prognosis, and survival in patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib. Ann Surg Oncol. 2012;19(5):1551–9.CrossRefPubMed
24.
Nozawa M, Yamamoto Y, Minami T, Shimizu N, Hatanaka Y, Tsuji H, et al. Sorafenib rechallenge in patients with metastatic renal cell carcinoma. BJU Int. 2012;110:E228–34.CrossRefPubMed
25.
Zama IN, Hutson TE, Elson P, Cleary JM, Choueiri TK, Heng DY, et al. Sunitinib rechallenge in metastatic renal cell carcinoma patients. Cancer. 2010;116(23):5400–6.CrossRefPubMed
Metadata
Title
Efficacy of rechallenge with BRAF inhibition therapy in patients with advanced BRAFV600 mutant melanoma
Authors
D. Viñal
D. Martinez
E. Espinosa
Publication date
01-08-2019
Publisher
Springer International Publishing
Keywords
Melanoma
Melanoma
Published in
Clinical and Translational Oncology / Issue 8/2019
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-018-02028-0

Other articles of this Issue 8/2019

Clinical and Translational Oncology 8/2019 Go to the issue

Research Article

Letrozole improves the sensitivity of breast cancer cells overexpressing aromatase to cisplatin via down-regulation of FEN1

Research Article

Efficacy of nivolumab as checkpoint inhibitor drug on survival rate of patients with relapsed/refractory classical Hodgkin lymphoma: a meta-analysis of prospective clinical study

Brief Research Article

Incidence of sleep problems and their mediating role on depression and anxious preoccupation in patients with resected, non-advanced cancer: data from NEOcoping study

Research Article

A comparative assessment of the effects of integrin inhibitor cilengitide on primary culture of head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines

Research Article

Identification a novel set of 6 differential expressed genes in prostate cancer that can potentially predict biochemical recurrence after curative surgery

Research Article

Positive nonsentinel lymph nodes are associated with poor survival in breast cancer: results from a retrospective study
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits