BRAF^V600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

Abstract

Background

Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer) or multiple myeloma harboring activating BRAF^V600 mutations for enrollment in a vemurafenib clinical study.

Methods

Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAF^V600 mutations by bidirectional direct Sanger sequencing.

Results

Overall incidence of BRAF^V600E mutation in evaluable patients (n=548) was 3% (95% confidence interval [CI], 1.7–4.7): 11% in colorectal tumors (n=75), 6% in biliary tract tumors (n=16), 3% in non-small cell lung cancers (n=71), 2% in other types of solid tumors (n=180), and 3% in multiple myeloma (n=31). There were no BRAF^V600 mutations in this cohort of patients with ovarian tumors (n=68), breast cancer (n=86), or prostate cancer (n=21).

Conclusion

This multicenter, national screening study confirms previously reported incidences of BRAF^V600 mutations from single-center studies. Patients identified with BRAF^V600 mutations were potentially eligible for enrollment in the VE-BASKET study.

Keywords:

• genetic testing
• proto-oncogene proteins B-raf
• PLX4032

Supplementary materials

Figure S1 CONSORT diagram.

Notes: ^aScreening population is defined as patients who had signed the informed consent. ^bEnrolled population is defined as patients who met the inclusion/exclusion criteria or provided the tumor samples. ^cEvaluable population is defined as enrolled patients with mutation results from the sampling/biopsy procedures.

Abbreviations: CNS, central nervous system; CRC, colorectal cancer; ECOG PS, Eastern Cooperative Oncology Group Performance Status; NSCLC, non-small cell lung cancer.

Table S1 List of other tumor types screened

Acknowledgments

The authors thank the patients who participated in this study and their families and loved ones for their support. They also thank the clinical trial teams for support in the execution of the trial. This study was funded by Genentech (a member of the Roche Group). The authors thank Bokai Xia, who provided the statistical programming support, and Jennifer M Kulak, PhD, and Melanie Sweetlove, MSc, of ApotheCom (San Francisco, CA), who provided writing services, funded by F Hoffmann-La Roche, Ltd. Igor Puzanov is currently affiliated with Roswell Park Cancer Institute, Buffalo, NY, USA.

Author contributions

B-MD and IP designed the study; ALC, B-MD, and IP collected the data; B-MD, SA, EM, TR, and IP analyzed the data; AC, B-MD, SA, EM, TR, and IP interpreted the data; SA conducted a literature search; B-MD and SA drafted the figures; and TR provided medical/clinical oversight during the course of the study. All authors contributed toward data analysis, drafting, and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

B-MD and EM are employees of and own stock in Genentech, Inc. SA and TR are employees of Genentech, Inc. IP is a consultant for Roche. ALC reports no conflict of interest in this work.