4117 - Efficacy of talimogene laherparepvec (T-VEC) in melanoma patients (pts) with locoregional (LR) recurrence, including in-transit metastases (ITM): subgroup analysis of the phase 3 OPTiM study

Background

ITM (defined as intralymphatic local, satellite, and regional cutaneous/subcutaneous metastases) is associated with significant morbidity; optimal therapy is poorly defined. T-VEC is an oncolytic immunotherapy approved for melanoma treatment based on results from the phase III OPTiM trial. This retrospective analysis of OPTiM assessed T-VEC in pts with unresectable AJCC 7 stage IIIB/C melanoma who had LR disease, including ITM, as the site of first recurrence following primary surgery.

Methods

In OPTiM, pts were randomised to intralesional T-VEC or subcutaneous recombinant GM-CSF. All pts were treated for ≥6 months, after which treatment was continued until clinically relevant disease progression, intolerability, consent withdrawal, complete response (CR), lack of response by 1 yr, or disappearance of injectable lesions (T-VEC arm only).

Results

109 patients (T-VEC n = 79; GM-CSF n = 30) had LR disease as the site of first recurrence (including ITM, local surgical scar, and regional lymph nodes). Most pts (63%) had ITM. Median time from primary melanoma diagnosis to first LR recurrence was 10.4 months. Time from first recurrence to randomisation into OPTiM was 6.6 months. At primary diagnosis, 45% of 109 pts had melanoma in the lower limbs, 25% in the head/neck, 15% on the trunk, and 11% upper limbs. At baseline, median age was 65 yrs, 94% had LDH ≤ULN, 76% had ECOG PS 0 and 35% had nodular melanoma. T-VEC vs GM-CSF led to objective response rates of 56% vs 1%, CR rates of 24% vs 0%, and durable response rates of 34% vs 0% (all p < 0.002 vs GM-CSF). Median OS was not reached with T-VEC vs 25 months with GM-CSF (HR, 0.48; 95% CI, 0.28–0.84; p = 0.0088). The LR subpopulation experienced higher T-VEC efficacy vs the entire study population (Table).Table:

1342P

Grouped term including in-transit/satellitosis (ITM), local surgical scar, and regional lymph nodes (LNs). 59 pts had ITM only as the site of 1^st recurrence, 17 had regional LNs only, 20 had surgical scar only, 2 had ITM AND regional LNs, 3 had surgical scar AND regional LNs, 5 had ITM AND surgical scar, and 3 pts had ITM, regional LNs AND surgical scar as the sites of 1^st recurrence.

HR, hazard ratio; ITT, intent-to-treat; KM, Kaplan-Meier; NR, not reported; OS, overall survival.

Conclusions

This analysis suggests that T-VEC may be of particular benefit in melanoma pts with LR recurrence, including ITM.

Clinical trial identification

NCT00769704.

Editorial acknowledgement

Ryan Woodrow, PhD, CMPP of Aspire Scientific (Bollington, UK), funded by Amgen (Europe) GmbH (Rotkreuz, Switzerland).

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

M.R. Middleton: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Immunocore; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Millennium; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Physiomics; Advisory / Consultancy, Research grant / Funding (institution): Rigontec; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Vertex; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Immunocore; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Millennium; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Physiomics; Advisory / Consultancy, Research grant / Funding (institution): Rigontec; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Vertex. K. Harrington: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD. M. Ross: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck ; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen. K. Ohrling: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. H. Radcliffe: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. F. Collichio: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck.