286P - First-line cobimetinib (C) + paclitaxel (P) in patients (pts) with advanced triple-negative breast cancer (TNBC): Updated results and tumoral immun...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Cytotoxic agents
Breast Cancer
Biological therapy
Presenter David Miles
Citation Annals of Oncology (2016) 27 (6): 68-99. 10.1093/annonc/mdw365
Authors D.W. Miles1, S. Kim2, T. Velu3, J.A. García-Saenz4, E. Tan-Chiu5, J.H. Sohn6, L. Dirix7, J. Vaňásek8, M.V. Borms9, J..I. Delgado Mingorance10, M. Liu11, M.M. Moezi12, M.F. Kozloff13, J.A. Sparano14, N. Xu15, Y. Yan16, M.J. Wongchenko17, B. Simmons18, V. McNally19, A. Brufsky20
  • 1Medical Oncology, Mount Vernon Cancer Centre, HA6 2RN - Northwood/GB
  • 2Oncology, Severance Hospital, Yonsei University Health System, Seoul/KR
  • 3Oncology, Chirec Cancer Institute CHIREC, 1180 - Brussels/BE
  • 4Medical Oncology, Hospital Clinico San Marcos, Madrid/ES
  • 5Research Director, Florida Cancer Research Institute, Plantation/US
  • 6Medical Oncology, Yonsei Severance Hospital Cancer Center, Seoul/KR
  • 7Cancer Center, Sint-Augustinuskliniek, Antwerp/BE
  • 8Radiation Oncology, Multiscan, s.r.o., Pardubice/CZ
  • 9Medical Oncology, AZ Groeninge Hospital, Kortrijk/BE
  • 10Medical Oncology/cicab Clinical Research Center, Hospital Infanta Cristina, Badajoz/ES
  • 11Hemato-oncology, Koo Foundation Sun Yat Sen Cancer Center, Taipei/TW
  • 12Clinical Research, Cancer Specialists of North Florida, Jacksonville/US
  • 13Medicine In Oncology/hematology, Ingalls Memorial Hospital, Harvey/US
  • 14Oncology, Montefiore Medical Center Albert Einstein College of Medicine, Bronx/US
  • 15Pd Biostatistics, Genentech, Inc., South San Francisco/US
  • 16Oncology Biomarker Development, Genentech, Inc., South San Francisco/US
  • 17Oncology Biomarker Development, Genentech, Inc., 94080 - South San Francisco/US
  • 18Product Development Oncology, Genentech, Inc., South San Francisco/US
  • 19Pdc, Roche Products Ltd., AL7 1TW - Welwyn Garden City/GB
  • 20Division Of Hematology-oncology, University of Pittsburgh, Pittsburgh/US



Resistance to standard taxane-based chemotherapy is common in TNBC. Preclinical data suggest that MEK inhibition may overcome taxane resistance and enhance antitumor immune response. The safety and efficacy of combining C, a highly selective MEK inhibitor, with P was explored in pts with metastatic/locally advanced TNBC and no prior systemic therapy for metastatic disease.


The COLET study (NCT02322814; EudraCT number, 2014-002230-32) consisted of a safety run-in (n ≈ 12) followed by a blinded 1:1 randomized stage (n ≈ 100 pts) to C + P or placebo (PBO) + P. Pts were treated with P 80 mg/m2 on days 1, 8, and 15 and C/PBO 60 mg/d on days 3-23 of each 28-d cycle. Gene expression and CD8 T-cell infiltration were measured by RNA-Seq and immunohistochemistry, respectively.


Sixteen women (median age, 55.5 years) were enrolled in the safety stage. At data snapshot (April 22, 2016), all 16 pts had received ≥1 dose of study treatment. Median time on treatment was 116 d (range, 7-336) for C and 84 d (range, 0-351) for P. 94% of pts had ≥1 adverse event (AE); most were grade 1/2 (Table). Ten pts (63%) had grade 3 AEs; there were no grade 4-5 AEs. Preliminary efficacy data from safety run-in included unconfirmed partial response (n = 8, 6 confirmed), stable disease (n = 4), and progressive disease (n = 2); 2 pts had not completed a tumor assessment. To date, matched pre- and post-treatment biopsies have been tested for 2 pts and demonstrate an increase in CD8 T-cell infiltration and PD-L1 expression with treatment in the basal subtype.

Most common (any grade ≥ 20%) AEs

Treatment-emergent AEs C + P (safety run-in stage), N = 16
All grades Grade ≥3
Diarrhea 10 (63) 1 (6)
Rash 8 (50) 0
Nausea 7 (44) 0
Blood CPK level increase 5 (31) 1 (6)
Alopecia 5 (31) 0
Stomatitis 4 (25) 2 (13)
Asthenia 4 (25) 1 (6)
Constipation 4 (25) 0
Dyspnea 4 (25) 0
Peripheral edema 4 (25) 0
Pyrexia 4 (25) 0
Vomiting 4 (25) 0

Abbreviations: AEs, adverse events; C, cobimetinib; CPK, creatinine phosphokinase; P, paclitaxel.


This is the first study to evaluate C + P in TNBC. The safety profile of C + P is consistent with that of known safety profiles. Initial data are consistent with previous reports on the immunomodulatory effects of MEK inhibition. Efficacy and safety will be further evaluated in the ongoing randomized stage.

Clinical trial identification

ClinicalTrials.gov ID NCT02322814; EudraCT number, 2014-002230-32

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.


This study was funded by F. Hoffmann-La Roche, Ltd.


D.W. Miles: Advisory Board, Honoraria, Investigator: Roche/Genentech. M.V. Borms: Consultant, grants: Roche. M-C. Liu: Consulting or Advisory Role: Roche, Pfizer. M.M. Moezi: Advisory Board: Millennium and BMS; Board of Directors: Cancer Specialists of North Florida; Investigator: Genentech and BMS; Speaker: Novartis, Millennium, BMS, and Pfizer. M.F. Kozloff: Advisory Board, Consultant, Investigator: Genentech/Roche; Speaker: Genentech. J.A. Sparano: Advisory Board: Genentech/Roche, Merrimack, AstraZeneca, Celgene, and Pfizer; Consultant: Metastat and Prescient Therapeutics; Research: Genentech/Roche, Takeda, Novartis, Merrimack, and Mediummune; Ownership Interest, Stock Options: Metastat. N. Xu: Employment, stock or other ownership: Roche. Y. Yan: Employment, stock or other ownership, patents, royalties, other intellectual property, travel, accommodations, expenses: Genentech/Roche. M.J. Wongchenko: Employment: Genentech; Stock or Other Ownership: Roche, ARIAD Pharmaceuticals. B. Simmons, V. McNally: Employment, stock or other ownership: Genentech.

A. Brufsky: Advisory board, honoraria, corporate-sponsored research: Genentech. All other authors have declared no conflicts of interest.