Efficacy of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated anaplastic thyroid cancer (ATC).

Author:

Subbiah Vivek1,Kreitman Robert J.2,Wainberg Zev A.3,Cho Jae Yong4,Schellens Jan H.M.5,Soria Jean-Charles6,Wen Patrick Y.7,Zielinski Christoph8,Urbanowitz Gladys9,Mookerjee Bijoyesh9,Wang Dazhe9,Rangwala Fatima A.9,Keam Bhumsuk10

Affiliation:

1. The University of Texas MD Anderson Cancer Center, Houston, TX;

2. National Institutes of Health, Bethesda, MD;

3. University of California, Los Angeles, Los Angeles, CA;

4. Yonsei University College of Medicine, Seoul, South Korea;

5. Netherlands Cancer Institute, Amsterdam, Netherlands;

6. Institut Gustave Roussy, Paris, France;

7. Dana-Farber Cancer Institute, Boston, MA;

8. Medical University of Vienna, Vienna, Austria;

9. Novartis Pharmaceuticals Corporation, East Hanover, NJ;

10. Seoul National University Hospital, Seoul, South Korea;

Abstract

6023 Background: ATC is a rare, aggressive malignancy with a dismal prognosis. Median overall survival (OS) is < 6 mo. Combined BRAF and MEK inhibition is efficacious in BRAF V600–mutated melanoma and lung cancer. One-fourth of ATCs harbor activating BRAF V600E mutations; thus, D (BRAF inhibitor) + T (MEK inhibitor) was evaluated as a treatment for pts with BRAF V600E–mutated ATC. Methods: In this phase 2, open-label trial (NCT02034110), pts with BRAF V600E mutations in 9 rare tumor types, including ATC, received continuous D (150 mg BID) + T (2 mg QD) until unacceptable toxicity, disease progression, or death. Eligible pts had advanced or metastatic cancer with no standard-of-care treatment options. The primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), OS, and safety. We report data from the ATC cohort. Results: 16 pts with BRAF V600E–mutated ATC had evaluable data with a median follow-up time of 47 wk (range 4-120 wk). BRAF V600E mutations were centrally confirmed in 15/16 pts. Median age was 72 y; all 16 pts had undergone prior tumor radiation and/or surgery and 6/16 pts (38%) had received ≥1 prior line of systemic therapy. Investigator-assessed confirmed ORR was 69% (11/16; 95% CI, 41%-89%), with 7/11 responses ongoing at the time of data cut. The Bayesian estimate of ORR was 69% (95% credible interval, 47%-87%) with a 100% probability that this ORR exceeded the 15% historical RR. Median DOR, PFS, and OS were not estimable due to insufficient progression and death events. Kaplan-Meier estimates of DOR, PFS, and OS at 12 mo were 90%, 79%, and 80%, respectively. The safety population comprised 100 pts enrolled in 7/9 histologies. Among all pts, 92% had an AE. Common AEs of any grade for all histologies were fatigue (38%), pyrexia (37%), and nausea (35%). In the ATC cohort, the most common grade 3/4 events were hyponatremia (19%), pneumonia (13%), and anemia (13%). Conclusions: D+T combination therapy significantly improved outcomes in ATC with a favorable safety profile. This regimen represents a clinically meaningful therapeutic advance for pts with advanced/metastatic BRAF V600–mutated ATC. Clinical trial information: NCT02034110.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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