Malignant Melanoma: Contemporary Management - Episode 13

Intralesional Therapy for Metastatic Melanoma


Jeffrey S. Weber, MD, PhD: Let’s go to the other end of the spectrum for a moment and turn back to Vern. We’re also going to hear, at this ASCO [American Society of Clinical Oncology Annual Meeting], about the long-term follow-up of the OPTiM study. This was the T-VEC [talimogene laherparepvec] versus GM-CSF [granulocyte-macrophage colony-stimulating factor]. And unlike Jason, I can’t quite pronounce the mouthful of its official name, so I’ll always call it T-VEC. But this was a trial that did lead to the registration of T-VEC based on 6-month PFS [progression-free survival]. What do we know about the follow-up? What has there been?

Vernon K. Sondak, MD: T-VEC is intralesional therapy, meaning you have to have a conveniently located—preferably cutaneous or subcutaneous—nodule to inject into. And we can use this therapy in 2 ways: alone or in combination. This study used T-VEC alone, and the goal was to make the injected lesions go away and to hope that sometimes there were uninjected lesions, even metastases, that would also go away because you stimulated an immune response in reaction to this injection. The OPTiM study showed it was better to inject lesions with T-VEC than what is essentially a placebo: the systemic injection of GM-CSF, not intralesional.

And the long-term data support that this is a treatment that is effective against the lesions that were injected. The longer-term results are disappointing in the sense that they don’t show a lot of efficacy at changing distant metastases. This isn’t a treatment that, for most patients, we’d want to use to inject a lesion in the hand to make a lung tumor go away. On the other hand, we might want to inject a lesion in the hand to stimulate an immune response, and give systemic therapy, and have a better chance of making that lung metastasis go away because the patient’s immune system is revved up. That’s a TBD, preview of hopefully coming attractions.

Jeffrey S. Weber, MD, PhD: That’s the MASTERKEY-265 trial, and hopefully that’s going to read out by ASCO next year.

Vernon K. Sondak, MD: Just to finish, there’s another way you could think about it. If all you have are a bunch of lesions on the skin, and you inject them all and they all go away, that patient is still at extraordinarily high risk of having a recurrence elsewhere. And we use adjuvant therapy for people with much lower risk. Giving combination therapy, then, is like giving adjuvant therapy after surgery. We want to think about both categories of the use of combination therapy as these new studies read out. Single-agent use of T-VEC is something that has value, predominantly in localized nondisseminated disease and particularly in patients who have medical comorbidities or social constraints that limit the use of systemic drugs. It’s a small percentage of our patients, but I think it’s important.

Transcript Edited for Clarity