Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Use of neoadjuvant intralesional talimogene laherparepvec (T-VEC) improves survival outcomes for patients undergoing surgery for stage IIIB–IVM1a melanoma, indicates research presented at the ESMO Congress 2022 in Paris, France.
Reinhard Dummer, from University Hospital Zurich in Switzerland, reported that the 5-year findings show a significant benefit in recurrence-free survival, event-free survival and overall survival with T-VEC followed by surgery versus surgery alone.
When session discussant Caroline Robert, from Gustave Roussy in Villejuif, France, compared the findings to trial results for other neoadjuvant therapies, such as nivolumab plus ipilimumab, she suggested that “T-VEC seems less effective”, but noted that the intralesional approach “is certainly much less toxic”.
Reinhard Dummer explained that 75 patients were randomly assigned to receive six doses of T-VEC followed by surgery between weeks 13 and 18 of the study, whereas 75 patients instead underwent surgery within 6 weeks of entering the study and received no neoadjuvant therapy.
All participants had at least one injectable and measurable subcutaneous or nodal lesion, a good ECOG performance status, and lactose dehydrogenase levels of no more than 1.5 ULN for those with stage IIIB/C disease or no more than 1.0 ULN for those with IVM1a melanoma. Patients were stratified by disease stage and planned adjuvant therapy – no adjuvant therapy was planned for over 80% of participants in either arm.
The presenter emphasized that the study had a “special patient population” with the inclusion of patients with stage IIIB in-transit, IIIC nodal and IIIC in-transit with nodal disease. The majority of patients in both the T-VEC and control arms had previously undergone surgery (93.4 vs 89.2%) and a small proportion had received radiation (5.3 vs 6.8%) or systemic therapy (5.3 vs 4.1%).
Reinhard Dummer explained that the primary endpoint of recurrence-free survival defined events as first local, regional or distant recurrence, death, withdrawal from the trial before surgery, and achievement of only R1 or R2 surgery.
The 5-year recurrence-free survival rate was 22.3% for patients given T-VEC plus surgery versus 15.2% for controls, giving a significant hazard ratio (HR) of 0.76 in favour of neoadjuvant therapy.
Event-free survival – measuring time to any recurrence before surgery or death – at 5 years was again significantly in favour of T-VEC, at 43.7% versus 27.4% for surgery alone and a HR of 0.57.
And 5-year overall survival was achieved by 77.3% of patients given T-VEC plus surgery versus 62.7% of controls, with a significant HR of 0.54.
The presenter said that 54.8% of patients given T-VEC went onto receive further anticancer treatment, as did 78.3% of controls. This included adjuvant immunotherapy, systemic immunotherapy, chemotherapy or targeted therapy with or without radiotherapy, and radiotherapy alone.
“These results suggest that an intratumorally administered oncolytic agent can elicit a meaningful long-term systemic effect and support neoadjuvant T-VEC plus surgery in advanced resectable melanoma”, he concluded.
Caroline Robert agreed that the “apparent OS superiority” of neoadjuvant T-VEC was not achieved by subsequent systemic therapy, noting that only 48% of patients received such treatment compared with 61% of controls.
However, she postulated that the statistical plan of the study was “debateable” with a “bias in randomization” and an “absence of visibility of the timing of events especially in [the T-VEC arm]”.
She also highlighted that the “very relaxed” alpha error confidence interval of 80% indicated that “the result is positive” but as the upper threshold of the confidence interval was 0.97, the results were “probably nonsignificant if a more standard 95% [confidence interval] had been chosen”.
Reference
LBA39 - Dummer R, Gyorki D, Hyngstrom J, et al. Final 5-year results of the phase II, multicentre, randomized, open-label trial of talimogene laherparepvec (T-VEC) neoadjuvant treatment plus surgery vs immediate surgery in patients with resectable stage IIIB-IVM1a melanoma. Ann Oncol 2022; 33 (suppl_7): S808–S869. Doi: 10.1016/annonc/annonc1089
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