1225PD - Prognostic impact of early complete metabolic response on FDG-PET, in BRAF V600 mutant metastatic melanoma patients treated with combination vemura...

Date 11 September 2017
Event ESMO 2017 Congress
Session Melanoma and other skin tumours
Topics Anti-Cancer Agents & Biologic Therapy
Cancer in Adolescents
Imaging, Diagnosis and Staging
Melanoma and other Skin Tumours
Presenter Wen Xu
Citation Annals of Oncology (2017) 28 (suppl_5): v428-v448. 10.1093/annonc/mdx377
Authors W. Xu1, J. Frederickson2, J. Callahan3, A. Ribas4, R. Gonzalez5, A.C. Pavlick6, O. Hamid7, T. Gajewski8, I. Puzanov9, A. Daud10, D. Colburn11, N. Choong2, M. Wongchenko12, R. Hicks3, G.A. McArthur1
  • 1Department Of Medical Oncology, Peter MacCallum Cancer Centre, 3000 - Melbourne/AU
  • 2., Genentech, Inc., 94080 - South San Francisco/US
  • 3Cancer Imaging, Peter MacCallum Cancer Centre, 3000 - Melbourne/AU
  • 4Department Of Medicine, Jonsson Comprehensive Cancer Center at UCLA, 90095-1781 - Los Angeles/US
  • 5., University of Colorado Comprehensive Cancer Centre, Aurora/US
  • 6Department Of Medicine, New York University, New York/US
  • 7-, The Angeles Clinic and Research Institute, 90025 - Los Angeles/US
  • 8Oncology, University of Chicago, Chicago, IL/US
  • 9Medical Oncology, Roswell Park Cancer Institute, Buffalo/US
  • 10Medical Oncology/hematology, University of California San Francisco UCSF, 94143 - San Francisco/US
  • 11Product Development, Genentech, Inc., 94080 - South San Francisco/US
  • 12Oncology Biomarker Development, Genentech Inc., 9408097124 - South San Francisco/US

Abstract

Background

Imaging with FDG-PET allows early recognition of metabolic response to targeted agents. We evaluated the timing of complete metabolic response (CMR) on PET as a predictor of clinical outcome in BRAF V600 mutant melanoma patients treated with vemurafenib and cobimetinb, as part of the BRIM-7 trial.

Methods

BRAF inhibitor naïve patients from BRIM-7 were included if they had evaluable PET scans at baseline, in cycle 1 (C1) (D10-15) and in C2 (D35-49). Metabolic response was evaluated by percentage injected dose (%ID). 52 of 63 BRAF-naïve patients were eligible for analysis (3 excluded - no C1 scan; 6 no C2 scan; 2 unevaluable scans due to excessive physiological muscle uptake). The primary aim was to evaluate the prognostic significance of an early CMR to combination vemurafenib and cobimetinib therapy. We divided patients into 3 groups, based on timing of CMR attainment.

Results

13 patients achieved CMR in cycle 1 (CMR1), 15 patients achieved CMR in cycle 2 (CMR2) and 24 patients did not achieve CMR within the first 2 cycles of treatment (noCMR). The median, 2 year and 3 year progression free survival (PFS) and overall survival (OS) of the 3 above groups are summarized in Table.Table:

1225PD

CMR1CMR2No CMR
Median PFS (yrs)Not reached1.11.0
2 yr PFS (%, 95% CI)83.9 (65.7-100)13.3 (3.7-48.4)37.5 (22.4-62.9)
3 yr PFS (%, 95% CI)71.9 (48.8-100)13.3 (3.7-48.4)18.8 (7.9-44.5)
Median OS (yrs)Not reached2.42.5
2 yr OS (%, 95% CI)84.6 (67.1-100)63.0 (41.5-95.8)58.3 (41.6-81.8)
3 yr OS (%, 95% CI)74.0 (52.2-100)21.0 (6.3-70.2)30.9 (16.5-57.9)

Patients achieving CMR1 had significantly better outcome than patients achieving CMR2 in terms of PFS (HR 0.18, 95% CI 0.05-0.62) and OS (HR 0.23, 95% CI 0.06-0.85). Similar results were observed comparing CMR1 over no CMR in PFS (HR 0.19, 95% CI 0.06-0.64) and in OS (HR 0.25, 95% CI 0.07-0.87). There was no difference between the CMR2 and noCMR groups in terms of PFS or OS.

Conclusions

Attainment of CMR on an early D10-14 PET was highly predictive of long-term survival with BRAF and MEK inhibition. However, attainment of CMR at a later time point at D35-49 did not appear predictive of a survival benefit. In fact, no difference in PFS or OS could be observed in patients who achieved CMR at D35-49, compared to those patients who did not attain CMR. Correlative science analysis to investigate the mechanism of these observations are underway.

Clinical trial identification

number: NCT01271803

Legal entity responsible for the study

Genentech Roche

Funding

Genentech Roche

Disclosure

J. Frederickson: Employer of Genentech and has Roche stocks D. Colburn, N. Choong, M. Wongchenko: Employee of Roche-Genentech. All other authors have declared no conflicts of interest.