Correlates of response and outcomes with talimogene laherperpvec

Abstract

Background and Objectives Patients with in‐transit or limited cutaneous metastatic melanoma may benefit from intralesional injections with talimogene laherparepvec (TVEC), a modified oncolytic herpesvirus. However, its use in patients with adverse prognostic scores in a real‐life clinical setting has not been studied. Methods We performed a two‐center retrospective analysis of 40 patients with metastatic melanoma treated with TVEC from 2015–2017. Demographics, overall response, and survival after therapy were noted. Results Overall, there was a durable response rate of 40%; median progression‐free survival (PFS) was 10.5 months and median overall survival (OS) was not reached. Bulky disease was associated with decreased OS (15.7 months vs not reached, P < .05) and mPFS (2.3 months vs not reached, P < .05), when compared with smaller tumors. Poor performance status (ECOG 2–3) was associated with worse OS (10.2 months vs not reached, P < .05) and PFS (2.1 months vs not reached, P < .05) compared to patients with ECOG 0–1. There was no difference in the outcomes with age greater than 75 or with prior therapies. Adverse events were relatively tolerable. Conclusions These findings demonstrate that TVEC is an effective and safe treatment for metastatic melanoma in a real‐life clinical setting, and suggest parameters to aid in appropriate therapy selection for optimal response.

Talimogene laherparepvec treatment to overcome loco-regional acquired resistance to immune checkpoint blockade in tumor stage IIIB–IV M1c melanoma patients

“…Based on a multivariate analysis in this trial, the cut-off for baseline tumor burden was > 14.5 cm [8]. The two-center retrospective analysis including 40 patients in USA reported increased overall survival and PFS in patients with smaller tumors [14]. The retrospective single-center analysis in 27 patients demonstrated decreased efficacy of T-VEC with increasing lesion size [13].…”

“…One patient with in-transit metastatic melanoma, stage IIIB (patient No 1) received T-VEC after prior targeted therapy with BRAF/MEK inhibitor and obtained a longlasting, complete response. Another patient (patient No 10) with M1a stage melanoma received prior anti-PD1-therapy, which led to a regression of lymph-node metastases, whereas in-transit metastases showed loco-regional resistance to Four patients with advanced melanoma, stage M1b-M1c, who had received one or more prior systemic therapies were treated with T-VEC (patients [11][12][13][14]. These patients suffered from a loco-regional progression, while distant metastases had been stable or regressive during prior systemic treatment.…”

“…Yet, published data about use of T-VEC in routine clinical practice are scarce. There are four recent case series from the US that report on use of T-VEC in three single institutions and one two-center retrospective analysis [11][12][13][14]. A recent multicenter chart review analyzed data from 27 patients treated with T-VEC in routine clinical practice in Germany [15].…”

Lesional therapies for in‐transit melanoma

“…16 However, in retrospective studies, the complete response rate was 39% to 40%. 17,18 To date, it has only been approved for use in the United States and more restrictive use in Europe. 22,23 In addition, the cost of many lesional therapies can be prohibitive.…”

A Retrospective Chart Review Study of Real-World Use of Talimogene Laherparepvec in Unresectable Stage IIIB–IVM1a Melanoma in Four European Countries

“…Since T-VEC approval in 2015, several retrospective studies have examined its use for the treatment of unresectable melanoma in realworld clinical practice in the USA [11][12][13][14][15] and Europe [16][17][18]. All found T-VEC to be well tolerated, with the most common AEs being mild influenza-like symptoms, e.g.…”