Talimogene laherparepvec (T-VEC; Imlygic) prior to surgery was associated with improved recurrence-free survival and overall survival compared with surgery alone in patients with resectable advanced melanoma.
John Hyngstrom, MD
Talimogene laherparepvec (T-VEC; Imlygic) prior to surgery was associated with improved recurrence-free survival (RFS) and overall survival (OS) compared with surgery alone in patients with resectable advanced melanoma, according to results from an open-label, phase II trial.1
Data presented in a poster at the 16th International Congress of the Society for Melanoma Research 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).
The 2-year RFS rate was 29.5% with T-VEC plus surgery compared with 16.5% with T-VEC alone (P =.07). Further, patients in the T-VEC arm had better outcomes despite receiving less subsequent therapy with checkpoint inhibitors.
“There’s an absolute improvement of about 14% in terms of RFS compared with surgery alone,” said study co-author John Hyngstrom, MD, an assistant professor of surgical oncology with the Huntsman Cancer Institute at the University of Utah. “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-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 ASCO Annual Meeting.2 The efficacy analysis shared at ASCO 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 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).
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 did not reach statistical significance.
Of the 57 patients in the T-VEC arm in the efficacy analysis, 13 (22.8%) had a pathologic complete response (pCR). The pCR rate was 17.1% (13 of 76) in the T-VEC arm in the intent-to-treat analysis.
Investigator-assessed clinical response in the T-VEC arm was 13.2% (10 of 76), including 5 of 13 patients who had pCR and 5 of the 63 who had less than pCR. The disease control rate (response plus stable disease) was 40.8% by ITT analysis, including 11 of 13 patients who had pCR and 20 of 63 patients who had less than pCR after T-VEC treatment.
The most commonly observed treatment-emergent adverse events (AEs) were flu-like symptoms.
Postoperative AE rates were 33.3% in the T-VEC group and 46.4% in the immediate-surgery group. Serious AEs (SAEs) 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 III/IV 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 pathologic complete response 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, that there might be [synergy] with a PD-1 inhibitor,” he added. “That would be the natural thing to combine with a PD-1 inhibitor.”