Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic colorectal cancer patients Journal Article


Authors: Yaeger, R.; Cercek, A.; O'Reilly, E. M.; Reidy, D. L.; Kemeny, N.; Wolinsky, T.; Capanu, M.; Gollub, M. J.; Rosen, N.; Berger, M. F.; Lacouture, M. E.; Vakiani, E.; Saltz, L. B.
Article Title: Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic colorectal cancer patients
Abstract: Purpose: BRAF-mutant metastatic colorectal cancer (mCRC) forms an aggressive subset of colorectal cancer with minimal response to selective RAF inhibitors. Preclinical data show that reactivation of EGFR signaling occurs in colorectal tumor cells treated with RAF inhibitors and that the addition of an EGFR inhibitor enhances antitumor activity. These data suggest that combined therapy with RAF and EGFR inhibitors could be an effective strategy for treating BRAF V600E mCRC. Experimental Design: We undertook a pilot trial to assess the response rate and safety of the BRAF inhibitor vemurafenib combined with anti-EGFR antibody panitumumab in patients with BRAF-mutant mCRC. Patients received standard approved doses of panitumumab and vemurafenib. Results: Fifteen patients were treated. Performance status was Eastern Cooperative Oncology Group (ECOG) 0 in 4 patients (27%) and ECOG 1 in 11 patients (73%). All patients had progressed through at least one standard treatment regimen, and 8 (53%) had received previous fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy. Treatment was well tolerated, with less cutaneous toxicity than would be expected with either agent, and no cases of keratoacanthomas/squamous cell carcinomas. Tumor regressions were seen in 10 of 12 evaluable patients with partial responses in 2 patients (100% and 64% regression lasting 40 and 24 weeks, respectively), and stable disease lasting over 6 months in 2 patients. Conclusions: Combined RAF and EGFR inhibition is well tolerated, with less cutaneous toxicity than would be expected with either agent, and results in modest clinical activity in this highly aggressive and chemoresistant subset of CRC. ©2015 AACR.
Keywords: signal transduction; adult; cancer chemotherapy; clinical article; controlled study; aged; clinical trial; drug tolerability; fatigue; neutropenia; squamous cell carcinoma; diarrhea; drug safety; skin toxicity; cancer patient; mutant protein; drug eruption; nausea; epidermal growth factor receptor; antineoplastic activity; irinotecan; panitumumab; arthralgia; hypomagnesemia; pruritus; cancer regression; pilot study; drug response; acne; tumor cell; cancer classification; oxaliplatin; hand foot syndrome; dry skin; alopecia; fluoropyrimidine; b raf kinase; photosensitivity; xerosis; keratoacanthoma; metastatic colorectal cancer; erythema multiforme; vemurafenib; keratosis; nose disease; human; male; female; priority journal; article; braf mutant metastatic colorectal cancer
Journal Title: Clinical Cancer Research
Volume: 21
Issue: 6
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2015-03-15
Start Page: 1313
End Page: 1320
Language: English
DOI: 10.1158/1078-0432.ccr-14-2779
PROVIDER: scopus
PUBMED: 25589621
PMCID: PMC5546416
DOI/URL:
Notes: Export Date: 4 May 2015 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Mario E Lacouture
    261 Lacouture
  2. Leonard B Saltz
    580 Saltz
  3. Neal Rosen
    363 Rosen
  4. Marc J Gollub
    106 Gollub
  5. Marinela Capanu
    206 Capanu
  6. Diane Lauren Reidy
    146 Reidy
  7. Rona Denit Yaeger
    64 Yaeger
  8. Eileen O'Reilly
    316 O'Reilly
  9. Michael Forman Berger
    380 Berger
  10. Efsevia Vakiani
    162 Vakiani
  11. Nancy Kemeny
    347 Kemeny