Highlights from

WCD 2019

World Congress of Dermatology

Milan 10-15 June 2019

Will malignant melanoma become a curable disease?

Melanoma therapy has been revolutionised. Five-year survival after metastatic cancer is a marker for highly likely continuous complete remission (CR), whereas 10-year survival after metastatic cancer is a marker for definitive cure [1,2]. In this respect, modern therapeutic options have proven to lead to a continuous CR, said Prof. Claus Garbe (Eberhard Karls University, Germany) [1].

In the COMBI-d and COMBI-v trials, first-line treatment with dabrafenib plus trametinib led to long-term benefit in approximately one third of the patients who had unresectable or metastatic melanoma with a BRAF V600E or V600K mutation [3]. More than a decade ago, the diagnosis of metastatic melanoma was still a death knell: long-term survival was non-existent, only 3% of patients survived for 5 years [4]. “The first glimmers of hope were seen in 2010, with the publication of data on ipilimumab and vemurafenib,” said Prof. Garbe. With the arrival of immunotherapy and targeted therapy, long-term survival was still rare in about 10-20% of patients [5,6]. The modern era of melanoma therapy started with combination therapy [3,7]. With the combination of encorafenib and binimetinib, 39% of patients survived 5 years [7]. However, as Prof. Garbe pointed out, this is by no means the end of the story: even more effective combinations are yet to come.

BRAF inhibition is known to increase T cell infiltration, melanoma antigen expression, and PD-1/PD-L1 expression, which may lead to synergistic activity with anti-PD-1 therapy. This was the rationale to assess therapy with the anti-PD-1 antibody spartalizumab in combination with dabrafenib and trametinib in previously untreated patients with advanced BRAF V600-mutant melanoma. [8]. In the COMBI-i trial, the triple therapy showed a promising and durable overall response rate of 75% with a CR in 33% of patients. With more than 15 months of follow-up, median progression-free survival was not reached. The safety profile was manageable.

“With these sophisticated multimodal combinations, we will probably reach long-term survival rates of 60 to 79%,” concluded Prof. Garbe.

When to stop therapy?

Prof. Caroline Robert (Institute Gustave Roussy, France) discussed the question whether therapy can be halted after patients reach CR [9]. With immunotherapy, this is obviously the case, as was shown by the long-term results of the KEYNOTE-001 study in patients who experienced CR with pembrolizumab [10]. Of 655 treated patients, 105 (16.0%) achieved CR after a median follow-up of 43 months. Therapy with pembrolizumab was discontinued by 91 patients (86.7%). The 24-month disease-free survival rate from time of CR was 90.9% in all 105 patients with CR and 89.9% in the 67 patients who discontinued pembrolizumab after CR. The low incidence of relapse after approximately 2 years from discontinuation provides hope for a cure–at least in some patients.

Unfortunately, this is different with targeted therapy. In a published case series of 12 patients with metastatic melanoma who achieved a CR and then ceased BRAF inhibitor-based therapy, 6 patients subsequently relapsed, and there were no predictors for disease recurrence [11]. However, all patients were suitable for subsequent therapy, including recommencing BRAF/MEK inhibitors with at least 2 out of 3 responding.

  1. Garbe C. 24th World Congress of Dermatology, 12 June 2019, Milan, Italy.
  2. Garbe C. 24th World Congress of Dermatology, 13 June 2019, Milan, Italy.
  3. Robert C, et al. N Engl J Med 2019 Jun 4; epub ahead of print.
  4. Korn EL, et al. J Clin Oncol 2008;26:527-34.
  5. Hodi FS, et al. N Engl J Med 2010;363:711–23.
  6. Sosman JA, et al. N Engl J Med 2012;366:707-14.
  7. Liszkay G, et al. J Clin Oncol 2019;37suppl: Abstract 9512.
  8. Long GV, et al. J Clin Oncol 2019;37suppl: Abstract 9531.
  9. Robert C. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.
  10. Robert C, et al. J Clin Oncol 2018;36:1668-1674.
  11. Carlino MS, et al. Br J Cancer 2016;115:1280-1284.

Top image: @ iStockPhoto: AzmanL

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.