A matching-adjusted indirect comparison of combination nivolumab plus ipilimumab with BRAF plus MEK inhibitors for the treatment of  BRAF -mutant advanced melanoma ☆

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Abstract

Background

Approved first-line treatments for patients with BRAF V600–mutant advanced melanoma include nivolumab (a programmed cell death protein 1 inhibitor) plus ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor; NIVO+IPI) and the BRAF/MEK inhibitors dabrafenib plus trametinib (DAB+TRAM), encorafenib plus binimetinib (ENCO+BINI), and vemurafenib plus cobimetinib (VEM+COBI). Results from prospective randomized clinical trials (RCTs) comparing these treatments have not yet been reported. This analysis evaluated the relative efficacy and safety of NIVO+IPI versus DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma using a matching-adjusted indirect comparison (MAIC).

Patients and methods

A systematic literature review identified RCTs for DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma. Individual patient-level data for NIVO+IPI were derived from the phase III CheckMate 067 trial ( BRAF-mutant cohort) and restricted to match the inclusion/exclusion criteria of the comparator trials. Treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using Cox proportional hazards and time-varying hazard ratio (HR) models. Safety outcomes (grade 3 or 4 treatment-related adverse events) with NIVO+IPI and the comparators were compared.

Results

In the Cox proportional hazards analysis, NIVO+IPI showed improved OS compared with DAB+TRAM (HR = 0.53; 95% confidence interval [CI], 0.39-0.73), ENCO+BINI (HR = 0.60; CI, 0.42-0.85), and VEM+COBI (HR = 0.50; CI, 0.36-0.70) for the overall study period. In the time-varying analysis, NIVO+IPI was associated with significant improvements in OS and PFS compared with the BRAF/MEK inhibitors 12 months after treatment initiation. There were no significant differences between NIVO+IPI and BRAF/MEK inhibitor treatment from 0 to 12 months. Safety outcomes favored DAB+TRAM over NIVO+IPI, whereas NIVO+IPI was comparable to VEM+COBI.

Conclusion

Results of this MAIC demonstrated durable OS and PFS benefits for patients with BRAF-mutant advanced melanoma treated with NIVO+IPI compared with BRAF/MEK inhibitors, with the greatest benefits noted after 12 months.

Highlights

•

First-line treatments for BRAF V600-mutant melanoma include NIVO+IPI and BRAF/MEK inhibitors.
•

Results from prospective RCTs comparing NIVO+IPI and BRAF/MEK inhibitors have not yet been reported.
•

This MAIC evaluated NIVO+IPI versus BRAF/MEK inhibitors for BRAF-mutant advanced melanoma.
•

OS and PFS benefits were noted with NIVO+IPI versus BRAF/MEK inhibitors beginning at 12 months.
•

These findings may provide information relevant to the selection of treatments for BRAF-mutant advanced melanoma.

Related collections

Most cited references 30

Record: found
Abstract: found
Article: not found

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez … (2015)

New England Journal of Medicine, 373(1), 23-34

0 comments Cited 1543 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez … (2019)

0 comments Cited 1276 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Final version of 2009 AJCC melanoma staging and classification.

Charles M. Balch, Jeffrey Gershenwald, Seng-jaw Soong … (2010)

To revise the staging system for cutaneous melanoma on the basis of data from an expanded American Joint Committee on Cancer (AJCC) Melanoma Staging Database. The melanoma staging recommendations were made on the basis of a multivariate analysis of 30,946 patients with stages I, II, and III melanoma and 7,972 patients with stage IV melanoma to revise and clarify TNM classifications and stage grouping criteria. Findings and new definitions include the following: (1) in patients with localized melanoma, tumor thickness, mitotic rate (histologically defined as mitoses/mm(2)), and ulceration were the most dominant prognostic factors. (2) Mitotic rate replaces level of invasion as a primary criterion for defining T1b melanomas. (3) Among the 3,307 patients with regional metastases, components that defined the N category were the number of metastatic nodes, tumor burden, and ulceration of the primary melanoma. (4) For staging purposes, all patients with microscopic nodal metastases, regardless of extent of tumor burden, are classified as stage III. Micrometastases detected by immunohistochemistry are specifically included. (5) On the basis of a multivariate analysis of patients with distant metastases, the two dominant components in defining the M category continue to be the site of distant metastases (nonvisceral v lung v all other visceral metastatic sites) and an elevated serum lactate dehydrogenase level. Using an evidence-based approach, revisions to the AJCC melanoma staging system have been made that reflect our improved understanding of this disease. These revisions will be formally incorporated into the seventh edition (2009) of the AJCC Cancer Staging Manual and implemented by early 2010.

0 comments Cited 1176 times – based on 0 reviews      Review now

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Author and article information

Contributors

A.A. Tarhini

Journal

Journal ID (nlm-ta): ESMO Open

Journal ID (iso-abbrev): ESMO Open

Title: ESMO Open

Publisher: Elsevier

ISSN (Electronic): 2059-7029

Publication date PMC-release: 06 February 2021

Publication date Collection: April 2021

Publication date (Electronic): 06 February 2021

Volume: 6

Issue: 2

Electronic Location Identifier: 100050

Affiliations

[1 ]Departments of Cutaneous Oncology and Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA

[2 ]Evidence Synthesis and Decision Modeling, Precision HEOR, Vancouver, Canada

[3 ]Medical Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA

[4 ]Department of Dermatology, Elbe Kliniken Buxtehude, Buxtehude, Germany

[5 ]Medical Oncology, The Royal Marsden Hospital, London, UK

[6 ]Medical Oncology, Dana-Farber/Harvard Cancer Center, Boston, USA

[7 ]US Health Economics and Outcome Research, Metastatic Melanoma, Bristol Myers Squibb, Princeton, USA

[8 ]Oncology Clinical Development, Bristol Myers Squibb, Princeton, USA

[9 ]Worldwide Health Economics and Outcomes Research, Melanoma, Bristol Myers Squibb, Uxbridge, UK

[10 ]Worldwide Health Economics and Outcomes Research, Melanoma, Bristol Myers Squibb, Princeton, USA

[11 ]Worldwide Medical, Melanoma, Bristol Myers Squibb, Princeton, USA

[12 ]Medical Oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA

Author notes

[∗ ] Correspondence to: Dr Ahmad A. Tarhini, H. Lee Moffitt Cancer Center and Research Institute, 10920 McKinley Drive, Tampa, FL 33612, USA. Tel: +813-745-8581 Ahmad.Tarhini@ 123456moffitt.org

Article

Publisher Item ID: S2059-7029(21)00004-1 Publisher ID: 100050

DOI: 10.1016/j.esmoop.2021.100050

PMC ID: 7872980

PubMed ID: 33556898

SO-VID: faa84c0f-154d-44ad-8563-e79eb23d214d

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).