Physician Views: Will Bristol-Myers Squibb's Opdivo/Yervoy combination gain traction in front-line melanoma?

Bristol-Myers Squibb may have gained US approval for the first combination therapy comprising two immuno-oncology agents – the PD-1 inhibitor Opdivo and the CTLA-4 inhibitor Yervoy; for the treatment of BRAF V600 wild type melanoma – but there remains some uncertainty as to how much usage it will garner. Versus Yervoy monotherapy, the combination has demonstrated significant improvements in median progression-free survival (PFS), but with some caveats.

ViewPoints: Bristol-Myers Squibb pushes first immuno-oncology combination past the approval post but will it prove a game-changer in melanoma?)

In patients who are low PD-L1 expressers, the combination demonstrated a median PFS of 11.2 months versus 5.3 months for Opdivo monotherapy and 2.8 months for Yervoy monotherapy. In patients classified as high expressers of PD-L1, however, median PFS was around 14 months regardless of whether Opdivo was administered alone or in combination with Yervoy, versus 2.8 months for Yervoy alone. Will PD-L1 testing therefore play a key role in guiding which patients are treated with the combination?

Improved efficacy is also countered by a higher incidence of grade 3 or 4 adverse events for the combination (54 percent) versus Yervoy monotherapy (24 percent) and a higher discontinuation rate: 47 percent versus 17 percent.

To better ascertain what impact the Opdivo/Yervoy combination will have in this treatment setting, we are asking US and EU5 oncologists the following questions…

The FDA has approved Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for the treatment of BRAF V600 wild-type unresectable or metastatic melanoma. What level of uptake do you anticipate for the combination in this setting?
None
Minimal
Moderate
Significant
Very significant

In a real-world setting, approximately what proportion of patients do you think will be able to handle the toxicity profile of the Opdivo/Yervoy combination? (incidence of grade 3 or 4 adverse events was 54 percent for the combination versus 24 percent for Yervoy monotherapy, while discontinuation rates were 47 percent for the combination versus 17 percent for Yervoy).

The Yervoy/Opdivo combination has demonstrated median PFS of 11.2 months versus 5.3 months for Opdivo monotherapy and 2.8 months for Yervoy monotherapy in PD-L1 low-expressing patients. In high expressing PD-L1 patients, median PFS was 14 months regardless of whether Opdivo was administered alone or in combination with Yervoy, versus 2.8 months for Yervoy. What role will PD-L1 testing play in determining whether this combination is used?
None
Minimal
Moderate
Significant
Very significant

What factor would most commonly prevent you from using the Opdivo/Yervoy combination in first-line melanoma patients?
Efficacy of PD-(L)1 monotherapy in this setting (when compared to toxicity of combo)
Lower efficacy among higher PD-L1 expressing patients (versus Opdivo monotherapy)
Toxicity of Opdivo/Yervoy combination
Cost of Opdivo/Yervoy combination
Lack of sufficiently understood biomarker to select patients best suited for therapy
Other (please state)

At this stage would you consider (and therefore be willing to use either drug) Opdivo and Keytruda as interchangeable with Yervoy in this setting?
Yes
No

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