Adjuvant T-VEC Is Superior to Surgery Alone in Melanoma

John Hyngstrom, MD

Adjuvant treatment with talimogene laherparepvec (T-VEC; Imlygic) in patients with resectable advanced melanoma demonstrated better recurrence-free survival (RFS) and overall survival (OS) compared with surgery alone, according to results of a study presented at a poster session at the 16th International Congress of the Society for Melanoma Research.¹

Data from the open-label, phase II trial showed that at a median follow-up of 31.2 months, the 2-year OS rate in the T-VEC arm was 88.9% versus 77.4% for surgery alone (HR, 0.49; 80% CI, 0.30-0.79; P = .05).

RFS rates at 2 years with T-VEC followed by surgery versus surgeryalone were 29.5% and 16.5%, respectively (P = .07). Despite receiving less subsequent therapy with checkpoint inhibitors, patients in the T-VEC arm had better outcomes.

“There’s an absolute improvement of about 14% in terms of RFS compared with surgery alone,” said study coauthor John Hyngstrom, MD, an associate professor of surgical oncology with the Huntsman Cancer Institute at the University of Utah in Salt Lake City. “What was surprising was that there was an improvement in 2-year OS, which [we] were not necessarily looking for.”

Investigators recruited 150 patients with high-risk, resectable stage IIIB to IVM1a melanoma at sites in 9 countries. Patients were then randomly assigned to immediate surgery (n = 74) or intralesional T-VEC followed by surgery at week 13 (n = 76).

Investigators previously presented 1-year results from the study at the 2019 American Society of Clinical Oncology Annual Meeting.²The efficacy analysis included 57 patients who received at least 1 dose of T-VEC and had surgery and 69 patients who had immediate surgery.

In the T-VEC arm, 33.5% of patients remained recurrence free at 1 year compared with 21.9% of patients who had surgery only (HR, 0.73; 80% CI, 0.56-0.93; P = .048). A sensitivity analysis that excluded positive surgical margins as an RFS event produced a larger difference in favor of neoadjuvant therapy (HR, 0.63; 80% CI, 0.47-0.83; P = .024).¹

More patients randomized to T-VEC were alive at 1 year (95.9% vs 85.8%; HR, 0.47; 80% CI, 0.27-0.82; P = .076), but at the time of the analysis, the difference had not reached statistical significance.¹

Of the 57 patients in the efficacy analysis treated on the T-VEC arm, 13 (22.8%) had a pathologic complete response (pCR). Patients in the intention-to-treat (ITT) population receiving T-VEC had a pCR rate of 17.1% (13 of 76).

Investigator-assessed clinical response in the T-VEC arm was 13.2% (10 of 76), including 5 of 13 patients who achieved pCR and 5 of the 63 who did not. The disease control rate, comprising all responses plus stable disease, was 40.8% in the ITT analysis, including 11 of 13 patients who had pCR and 20 of 63 patients who did not following T-VEC treatment.

The most commonly observed treatment-emergent adverse events (AEs) were flulike symptoms.

Postoperative AE rates were 33.3% in the T-VEC group and 46.4% in the immediate-surgery group. Serious AEs (SAEs) post surgery occurred in 14.0% of the T-VEC group and 2.9% of the immediate-surgery arm. Grade 3 SAEs in the T-VEC group consisted of 2 cases of cellulitis and 1 case each of anembryonic gestation, cholecystitis, device occlusion, influenza, and wound infection. In the immediate-surgery group, grade 3 SAEs consisted of 1 case each of peripheral embolism and wound abscess.

Hyngstrom said the ongoing phase Ib/III MASTERKEY-265/KEYNOTE-034 trial (NCT02263508) is evaluating patients with unresectable stage IIIB/IVM1 disease assigned to pembrolizumab (Keytruda) plus T-VEC or placebo. That study has not reported data yet, but he said combining a checkpoint inhibitor with T-VEC in a neoadjuvant setting could result in improved pCR and RFS.

“There’s some correlative evidence that would suggest that, certainly in patients where we can detect CD8+ cell density or PD-L1 expression, there might be [synergy] with a PD-1 inhibitor,” Hyngstrom said. “That would be the natural thing to combine with a PD-1 inhibitor.”

References:

1. Dummer R, Gyorki DE, Hyngstrom J, et al. Improved recurrence-free survival (RFS) from a randomized phase 2 study of neoadjuvant (neo) talimogene laherparepvec (T-VEC) plus surgery (surg) vs surg for resectable stage IIIB-IVM1a melanoma (MEL). Pigment Cell Melanoma Res. 2020;33(1):148-255. doi: 10.1111/pcmr.12834.
2. Dummer R, Gyorki DE, Hyngstrom J, et al. One-year (yr) recurrence-free survival (RFS) from a randomized, open label phase II study of neoadjuvant (neo) talimogene laherparepvec (T-VEC) plus surgery (surgx) versus surgx for resectable stage IIIB-IVM1a melanoma (MEL). J Clin Oncol. 2019;37(suppl 15; abstr 9520). doi: 10.1200/ JCO.2019.37.15_suppl.9520.