Dr. Reinhard Dummer
T-VEC is a modified virus that lyses tumor cells locally and induces a systemic immune response. In the phase 2 trial, neoadjuvant T-VEC plus surgery improved 3-year recurrence-free survival, when compared with immediate surgery, in patients with resectable melanoma.
“This is the first neoadjuvant trial for an approved oncolytic virus in melanoma and the largest randomized prospectively controlled neoadjuvant melanoma trial completed to date,” said investigator Reinhard Dummer, MD, of University Hospital Zürich.
The multicenter trial enrolled 150 patients with resectable stage IIIB–IV M1a melanoma (thereby including many with in-transit metastasis) who had at least one injectable lesion.
“This patient population is typically excluded from the trials that are published. Those trials typically focus on lymph node metastasis only,” Dr. Dummer noted.
The patients were randomized evenly to receive six doses over 12 weeks of intralesional T-VEC followed by surgical resection, or to the conventional approach of immediate surgical resection.
Survival results
The median follow-up for this interim analysis was 41.3 months.
The 3-year rate of recurrence-free survival, the trial’s primary endpoint, was 46.5% with T-VEC plus surgery and 31.0% with immediate surgery (hazard ratio, 0.67; P = .043). The median duration of recurrence-free survival was 27.5 months and 5.4 months, respectively.
These results were comparable with results seen at 2 years, which were published in Annals of Oncology in 2019. The 2-year rate of recurrence-free survival was 50.5% with T-VEC plus surgery and 31.0% with immediate surgery (HR, 0.66; P = .038).
“These patients appear to be in a plateau phase now,” Dr. Dummer remarked.
The 3-year rate of event-free survival, which excluded any events related to a delay of surgery, was 50.3% for T-VEC and 32.7% for immediate surgery (HR, 0.58, P = .015).
Findings for both outcomes were similar when analyses were repeated after removing events that occurred after receipt of therapy in the adjuvant or metastatic setting.
Finally, the 3-year rate of overall survival was 83.2% with T-VEC plus surgery and 71.6% with immediate surgery (HR, 0.54; P = .061). Respective 2-year values were 88.9% and 77.4% (HR, 0.49; P = .050).
In all, 50.7% of patients in the T-VEC group received subsequent anticancer therapy, compared with 76.8% in the immediate-surgery group. Respective values specifically for subsequent immunotherapy – usually immune checkpoint inhibitors – were 32.9% and 46.4%.
“I think this is a good argument that the effects we see on overall survival and recurrence-free survival are not caused by improved second-line treatments,” Dr. Dummer said.
No new safety signals emerged during the additional year of follow-up. The trial’s final analysis will be conducted after 5 years of follow-up.
“These results build upon the prior 2-year results to support the potential beneficial effect of neoadjuvant T-VEC on advanced resectable melanoma,” Dr. Dummer said.
“In general, if you compare this to the objective outcomes that we see with neoadjuvant ipilimumab-nivolumab, for example, the results do not look very attractive,” he acknowledged.
“However, we have to keep in mind that this is a difficult patient population,” he added, noting that many patients have in-transit metastases that would disqualify them from conventional neoadjuvant therapy. Also, cross-trial comparisons are complicated by the need to allow adjuvant therapy in patients who receive neoadjuvant therapy.
“I would say the combination of ipilimumab-nivolumab should be more powerful, but T-VEC has some impact, and from my understanding, T-VEC would be a perfect partner for a combination, for example, with an anti–[programmed death 1] agent,” Dr. Dummer concluded.