Novartis scores but Roche misses in melanoma trials

A phase III trial of Novartis Tafinlar and Mekinist has confirmed the potential of the pair in the post-surgical treatment of melanoma, but Roche was unable to match that in a trial of its Zelboraf candidate.

The two studies reported at the European Society of Clinical Oncology (ESMO) congress in Madrid this week were carried out in high-risk, early-stage patients with stage III BRAF V600E/K mutation-positive melanoma who had undergone surgery to remove tumour tissue. The drugs were given after surgery to try to destroy residual cancer cells and prevent recurrence.

The combination of Novartis BRAF inhibitor Tafinlar (dabrafenib) and MEK inhibitor Mekinist (trametinib) met its objective with a 53% reduction in death or disease recurrence in the COMBI-AD trial, which lead investigator Axel Hauschild of the University of Kiel, Germany described as "unprecedented" in this patient population.

He suggested that the data - which has also just been published in the New England Journal of Medicine and showed that Tafinlar/Mekinist doubles the relapse-free survival time versus placebo - indicates that the drugs could "transform the standard of care in the melanoma adjuvant setting".

Novartis plans to move swiftly with regulatory filings for Tafinlar/Mekinist later this year in adjuvant melanoma treatment in BRAF-positive patients, who account for around 50% of the total population with this type of skin cancer. If approved, it will provide an alternative to interferon - which is toxic and of limited efficacy - and Bristol-Myers Squibb's Yervoy (ipilimumab) which, while it can boost survival, has side-effect issues.

The duo is also approved for use in patients whose tumours are not treatable with surgery, as well as in BRAF-positive non-small cell lung cancer, and brought in $403m in sales in the first half of 2017.

"Both ipilimumab and the combination of dabrafenib plus trametinib have improved overall survival compared to placebo," commented Olivier Michielin, ESMO melanoma faculty coordinator. "We now need to determine which adjuvant strategy is best suited for which patient, while also factoring in the upcoming results of PD-1 blockade in that setting."

In the same ESMO session, Roche's BRIM8 trial of BRAF inhibitor Zelboraf (vemurafenib) as adjuvant treatment for patients with resected BRAF-mutant melanoma at high risk for recurrence failed to hit its primary objective of extending disease-free survival (DFS) in stage IIIc disease, although it did show a 46% improvement on this measure in less advanced (stage IIb-IIIc) tumours.

Roche said that the finding that the drug was less effective in more severe disease was a surprise, and that it would discuss the data with regulators. Zelboraf is generally prescribed alongside Roche's MEK inhibitor Cotellic (cobimetinib) in melanoma, but the BRIM8 data suggest Novartis' pair is heading for dominance in the targeted end of adjuvant treatment of BRAF-positive patients.