OPTiM Follow-up Shows Improved CR Rate With T-VEC in Melanoma

Robert Andtbacka, MD

A retrospective analysis of the phase III OPTiM study found that treatment with talimogene laherparepvec (T-VEC; Imlygic) resulted in complete responses (CR) in 17% of patients seen in all stages of melanoma. Median time to achieve a CR was 8.6 (6.0—13.6) months. A high proportion of response occurred in patients with early-stage disease and lower tumor burden, according to study authors.¹

In OPTiM, a phase III trial in 436 patients with unresected stage IIIB to IV melanoma, T-VEC improved durable response rates from 2.1% to 16.3% versus subcutaneous GM-CSF. Overall response rates (ORR) for T-VEC and GM-CSF were 26.4% and 5.7%, respectively. Median overall survival (OS) was 23.3 months with T-VEC and 18.9 months with GM-CSF (HR, 0.79; 95% CI, 0.62—1.00; P = .051).

The OPTiM study was the basis of the October 2015 FDA approval of T-VEC for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with recurrent melanoma after initial surgery. T-VEC is herpes simplex virus type 1-derived injectable oncolytic virus.

OncLive spoke with Robert Andtbacka, MD, associate professor, Division of Surgical Oncology, Department of Surgery at the University of Utah School of Medicine, the lead study author on the retrospective analysis.

OncLive: What prompted this analysis?

In his interview, Andtbacka explains the goals of the analysis, the significance of its results, and the future for T-VEC in melanoma.Andtbacka: The cutoff for the primary analysis of the OPTiM trial was in December 2012. After that cutoff, patients were followed and other secondary analyses occurred later on.

This included the final overall survival analysis, which occurred in September 2014. We knew that, in the December 2012 analysis, there were a number of patients who had CR with T-VEC. We also knew that there were other patients who continued on treatment who may have had a CR after that analysis.

What were the findings?

We were interested in determining if there were additional patients who had a CR with a longer follow-up, and also to try and determine what factors led them to have that CR.There were 287 patients who were treated with T-VEC. When we followed those patients after September 2014, 50 of them, or 17%, actually had a CR on the therapy. We had 43 patients, or 15%, who had a partial response (PR). Out of all the patients treated with T-VEC, 1 out of every 6 patients actually had a CR to treatment.

We then tried to determine who the patients were who were likely to have a CR. We found out that those with stage IIIb, IIIc, or stage IV M1a disease were most likely to have a CR, with almost an 8-fold increase probability than patients who had stage IV M1b and M1c disease. Patients with a tumor burden that was lower than the median tumor burden were more also likely to have a CR.

What this means is that patients with earlier disease, stage IIIb, IIIc, and stage IV M1a, have a very good probability of having not only a response, but also a CR to T-VEC.

What should oncologists take away from these findings?

We found that if patients have a CR, the probability of that response lasting for 18 months or longer was 72%. We also found that, in patients who had a CR, the recurrence-free survival after 3 years was 78%. The overall survival in patients that had a CR after 5 years was almost 90%.We should consider T-VEC as a potential monotherapy in patients with earlier stage disease. In patients with more advanced disease, some did have a CR; however, this occurred at much lower rates.

What do you see on the horizon for the use of T-VEC?

For these patients, we should consider using T-VEC in combination. We are doing studies on this right now, where we are combining T-VEC with checkpoint inhibitors, specifically to try and generate a CR in these types of patients.T-VEC is associated with pretty good data for patients with advanced melanoma who have an injectable lesion. It appears to be very well tolerated by patients. We have had very few grade 3 or 4 toxicities from the treatment. For patients with comorbidities, who may not be eligible for other treatments, T-VEC has tremendous potential.

Specifically, if you look at the cases where patients have had earlier disease, the response rate to T-VEC is very, very good. Some would argue—although they’ve never been compared head-to-head—that T-VEC is even better than checkpoint inhibitors. T-VEC may, for some patients, produce a better response.

1. Andtbacka R, Kaufman H, Collichio F, et al. Durable complete responses (CRs) in patients (pts) with stage IIIB-IV melanoma treated with talimogene laherparepvec. Presented at: Society of Surgical Oncology 69th Annual Cancer Symposium; Boston, Massachusetts; March 2-5, 2016.