Single versus combination immunotherapy drug treatment in melanoma

ABSTRACT

Introduction: The advent of new immunotherapies for the treatment of metastatic melanoma has resulted in various novel combination strategies. Because of their distinct modes of action, different immunotherapies have been investigated in combination with one another, as well as combined with targeted therapies and other treatment modalities.

Areas covered: Anti-CTLA-4 and anti-PD-1 treatments enhance antitumor immunity through complementary and non-redundant mechanisms. The combination of the anti-CTLA-4 agent ipilimumab and the anti-PD-1 agent nivolumab has been shown to improve progression-free survival and objective response rate compared with either agent alone as monotherapy in patients with advanced melanoma. However, the combination was associated with significant toxicity, with around one-third of patients discontinuing treatment as a result. The sequential use of nivolumab and ipilimumab was associated with similar outcomes and comparable toxicity to concurrent therapy. Clinical trials assessing various combinations of immunomodulating antibodies are ongoing or planned. Ipilimumab and pembrolizumab have also been investigated in combination with the oncolytic virus, talimogene laherparepvec (T-VEC), with promising results. In addition, immunotherapies have also been combined with chemotherapy, radiotherapy and electrochemotherapy.

Expert opinion: Investigation of combination approaches represents the start of a new story that begins with melanoma treatment and expands to embrace other solid and hematological cancers.

KEYWORDS:

• Immunotherapy
• anti-CTLA-4
• ipilimumab
• anti-PD1
• nivolumab
• combination therapy
• melanoma

Article highlights

• The combination of the anti-CTLA-4 agent ipilimumab and the anti-PD-1 agent nivolumab has been shown to improve progression-free survival and objective response rate compared with either agent alone as monotherapy in patients with advanced melanoma.

• However, the combination was associated with significant toxicity, with around one-third of patients discontinuing treatment as a result.

• The sequential use of nivolumab and ipilimumab was associated with similar outcomes and comparable toxicity to concurrent therapy.

• Ipilimumab and pembrolizumab have also been investigated in combination with the oncolytic virus, talimogene laherparepvec, with promising results.

• Combining immunotherapy with chemotherapy, radiotherapy or electrochemotherapy has also shown potential.

This box summarizes key points contained in the article.

Declaration of interest

A Grimaldi has received honoraria from Bristol-Myers Squibb, Roche Genentech, Novartis and GlaxoSmithKline. P Ascierto has participated in a consultancy/advisory role for Bristol-Myers Squibb, Roche, Merck Sharpe and Dohme, Ventana, Novartis and Amgen, and received research funds from Bristol-Myers Squibb, Roche and Ventana. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.