2019 ASCO Annual Meeting!
Session: Melanoma/Skin Cancers
Type: Oral Abstract Session
Time: Tuesday June 4, 9:45 AM to 12:45 PM
Five-year analysis on the long-term effects of dabrafenib plus trametinib (D + T) in patients with BRAF V600–mutant unresectable or metastatic melanoma.
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 9507)
Author(s): Paul D. Nathan, Caroline Robert, Jean Jacques Grob, Daniil Stroyakovskiy, Boguslawa Karaszewska, Axel Hauschild, Eugeny Levchenko, Vanna Chiarion Sileni, Jacob Schachter, Claus Garbe, Igor Bondarenko, Michael A. Davies, Antoni Ribas, Keith Flaherty, Paul Burgess, Monique Tan, Eduard Gasal, Dirk Schadendorf, Georgina V. Long; Mount Vernon Cancer Centre, Northwood, United Kingdom; Paris-Sud University, Gustave Roussy, Villejuif Cedex, France; AIX-Marseille University, Marseille, France; Moscow City Oncology Hospital, Moscow, Russian Federation; Przychodnia Lekarska KOMED, Konin, Poland; University Hospital Schleswig-Holstein, Kiel, Germany; Petrov Research Institute of Oncology, St. Petersburg, Russia; Melanoma Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy; Ella Lemelbaum Institute for Immuno-Oncology and Melanoma, Sheba Medical Center, Tel-Hashomer, and Sackler Medical School, Tel-Aviv University, Tel-Aviv, Israel; Department of Dermatology, University of Tübingen, Tübingen, Germany; Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; The University of Texas MD Anderson Cancer Center, Houston, TX; University of California, Los Angeles, Los Angeles, CA; Dana-Farber Cancer Institute/Harvard Medical School and Massachusetts General Hospital, Boston, MA; Novartis Pharma AG, Basel, Switzerland; Novartis Pharmaceuticals Corporation, East Hanover, NJ; Department of Dermatology, University Hospital Essen, Essen, Germany; Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, Australia
Background: First-line treatment with D+T demonstrated prolonged progression-free survival (PFS) and overall survival (OS) in patients with BRAF V600–mutant unresectable or metastatic melanoma. With 5 years of follow-up, we report survival and describe characteristics of patients in the phase 3 COMBI-d and COMBI-v trials with long-term benefit. Methods: Pooled 5-year landmark data for patients treated with D+T in the phase 3 COMBI-d (NCT01584648) and COMBI-v (NCT01597908) trials were analyzed. The trials enrolled patients with previously untreated BRAF V600E/K–mutant unresectable or metastatic melanoma. Patients received D 150 mg twice daily plus T 2 mg once daily vs either D + placebo (COMBI-d) or vemurafenib (COMBI-v). The primary endpoints were PFS in COMBI-d and OS in COMBI-v. Results: The pooled population included 563 patients who received D+T (COMBI-d, n = 211; COMBI-v, n = 352). Four- and 5-year PFS and OS rates were similar, suggesting a stabilization (4- and 5-year PFS, 21% [95% CI, 17%-24%] and 19% [95% CI, 15%-22%, respectively]; 4- and 5-year OS, 37% [95% CI, 33%-42%] and 34% [95% CI, 30%-38%], respectively). In patients with normal baseline lactate dehydrogenase (LDH) levels the 5-year PFS rate was 25% vs 8% in patients with elevated baseline LDH levels. Similarly, the 5-year OS rate was considerably higher in patients with normal baseline LDH levels vs those with elevated LDH levels at baseline (43% vs 16%). Among patients with normal baseline LDH levels and < 3 organ sites with metastases, the 5-year PFS and OS rates were 31% and 55%, respectively. In addition, exploratory analyses will be performed to characterize subgroup(s) of patients most likely to experience long-term benefit. Of 299 patients who received subsequent anticancer therapy following treatment with D+T, 151 (51%) received an anti–CTLA-4 therapy and 102 (34%) received an anti–PD-1 therapy. The safety profile of D+T was as previously reported, and no new safety signals were observed. No treatment-related deaths were reported. Conclusions: First-line treatment with D+T leads to durable long-term benefit in many patients with BRAF V600–mutant unresectable or metastatic melanoma. Clinical trial information: NCT01584648; NCT01597908