Robert Andtbacka, MD, associate professor in the Division of Surgical Oncology, Department of Surgery at the University of Utah School of Medicine, discusses the optimal use of talimogene laherparepvec (T-VEC; Imlygic) in patients with melanoma.

As reported in the OPTiM study, the trial that led to the FDA approval of T-VEC, the agent was found to elicit more responses in the population of patients with regional disease. This is an underserved area, Andtbacka explains, as several clinical trials do not include patients with this disease stage.

This demonstrates that oncolytic immunotherapy agents, such as T-VEC, are effective in these patients. However, it should be recognized that other checkpoint inhibitors also have activity in this population, although there has never been a head-to-head comparison of them to T-VEC, he adds.

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Robert Andtbacka, MD, associate professor in the Division of Surgical Oncology, Department of Surgery at the University of Utah School of Medicine, discusses the optimal use of talimogene laherparepvec (T-VEC) in patients with melanoma.

Dr. Andtbacka on Optimal Use of T-VEC in Melanoma

Robert Andtbacka, MD, associate professor, Division of Surgical Oncology, Department of Surgery, University of Utah School of Medicine, discusses ongoing clinical trials investigating oncolytic immunotherapies as treatment for melanoma.

Oncolytic immunotherapies have been a research focus in the field of melanoma for the past few years, Andtbacka says. The agents, which are injected directly into tumors, are being investigated as both monotherapy and as part of combination regimens.

Andtbacka says oncolytic immunotherapies are also being studied in the neoadjuvant setting for patients with resectable disease.

Robert Andtbacka, MD, associate professor, Division of Surgical Oncology, Department of Surgery, University of Utah School of Medicine, discusses ongoing clinical trials investigating oncolytic immunotherapies as a treatment for melanoma.

Dr. Andtbacka on Ongoing Trials With Oncolytic Immunotherapies in Melanoma

Robert H. I. Andtbacka, MD, CM, a surgeon and investigator with Intermountain Healthcare and Huntsman Cancer Institute, discusses the safety and efficacy of talimogene laherparepvec (T-VEC) in combination with ipilimumab in patients with previously untreated, unresected stage IIIB-IV melanoma.

In a phase Ib study, 18 patients received treatment with the combination of T-VEC and the CTLA-4 inhibitor ipilimumab. Overall, this study demonstrated promising efficacy without inducing dose-limiting toxicity, with most of the toxicity experienced by patients associated with ipilimumab rather than T-VEC, Andtbacka explains. Overall, grade 3/4 adverse events occurred in 32% of patients, with the most common T-VEC-related event being pyrexia.

The overall response rate for ipilimumab plus T-VEC was 56%, with 33% of patients experiencing a complete response. The disease control rate was 72%. The ongoing phase Ib study is moving into a phase II component that will randomize patients to ipilimumab alone or in combination with T-VEC, explains Andtbacka. This study is currently recruiting patients (NCT01740297). 

Robert H. I. Andtbacka, MD, CM, from Intermountain Healthcare and Huntsman Cancer Institute, discusses the safety and efficacy of T-VEC in combination with ipilimumab in patients with previously untreated, unresected stage IIIB-IV melanoma.

Dr. Andtbacka on T-VEC Plus Ipilimumab in Unresected Melanoma

Robert H. I. Andtbacka, MD, CM, a surgeon and investigator with Intermountain Healthcare and Huntsman Cancer Institute, discusses overall survival (OS) findings from the phase III OPTiM study that explored the intralesional injection talimogene laherparepvec (T-VEC) in patients with unresectable melanoma.

The phase III OPTiM study compared T-VEC with GM-CSF in 436 patients with unresected stage IIIB/C and IV melanoma. At the primary survival analysis, the median OS was 23.3 months with T-VEC compared with 18.9 months for GM-CSF (HR = 0.787; 95% CI, 0.62-1.00; 

 = .051). The durable response rate with T-VEC was 16% versus 2% for GM-CSF.

The 4.4-month difference in survival is clinically significant, but narrowly missed statistical significance, Andtbacka suggests. The lack of significance could be the result of the study not being adequately powered to look at a small difference in OS, since survival was a secondary endpoint. Clinically, Andtbacka believes the median survival and the durability of response is more important for determining treatment.

The therapies received following progression on the trial were similar between the two arms, Andtbacka notes. In a subanalysis, it was found that more patients in the T-VEC group had advanced stage IV M1b/M1c disease compared with the GM-CSF, suggesting a worse outcome. Additionally, a higher number of patients with ECOG performance status 1 compared with 0 were enrolled into the T-VEC group versus GM-CSF, Andtbacka notes.

View more from the 2014 ASCO Annual Meeting

Robert H. I. Andtbacka, MD, CM, from the Huntsman Cancer Institute, discusses OS findings from the phase III OPTiM study that explored T-VEC in patients with unresectable melanoma.

Dr. Andtbacka Discusses OS With T-VEC in Melanoma

Robert Andtbacka, MD, a surgeon and investigator with Intermountain Healthcare and Huntsman Cancer Institute, provides an overview of the phase III OPTiM trial that explored treatment with talimogene laherparepvec (T-VEC) in patients with advanced melanoma.

In the trial, 436 patients with unresected stage IIIB/C and IV melanoma were randomized 2:1 to intralesional T-VEC or subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). The primary endpoint of the trial was durable response rate (DRR), which was defined to include a continuous partial or complete response for greater than 6 months. Overall, patients treated with T-VEC experienced a DRR of 16% compared to 2% for GM-CSF.

The secondary endpoint of the trial was overall survival (OS), Andtbacka notes. At a planned interim analysis a trend toward an improvement in OS was observed in favor of T-VEC, with a hazard ratio of 0.79 (95% CI: 0.61, 1.02). This analysis was derived from 250 of the planned 290 events with a full analysis expected later this year.

Robert Andtbacka, MD, from the Huntsman Cancer Institute, provides an overview of the phase III OPTiM trial that explored treatment with talimogene laherparepvecin patients with advanced melanoma.

Robert H. I. Andtbacka, MD

Articles

Dr. Andtbacka on Optimal Use of T-VEC in Melanoma

Dr. Andtbacka on Ongoing Trials With Oncolytic Immunotherapies in Melanoma

Dr. Andtbacka on T-VEC Plus Ipilimumab in Unresected Melanoma

Dr. Andtbacka Discusses OS With T-VEC in Melanoma

Dr. Andtbacka Reviews the Efficacy of T-VEC in Melanoma