Results of a phase II, open‐label, non‐comparative study of intralesional PV‐10 followed by radiotherapy for the treatment of in‐transit or metastatic melanoma

Abstract

BACKGROUNDIn‐transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T‐cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction.METHODSAn open‐label, single‐arm phase II study was performed to assess the efficacy and safety of PV‐10 followed by hypofractionated radiotherapy. Patients had in‐transit melanoma metastases suitable for IL therapy and radiotherapy.RESULTSFifteen patients were enrolled and thirteen completed both treatment components. The overall response rate was 86.6% and the clinical benefit was 93.3% on an intention to treat analysis (CR 33.3%, PR 53.3%, SD 6.7%). The median follow up duration was 19.25 months. Size of metastases (<10 mm) predicted lesion complete response (74.6%). Treatment was well tolerated with no associated grade 4 or 5 adverse events.CONCLUSIONSThe combination of PV‐10 and radiotherapy resulted in lesion‐specific, normal tissue‐sparing, ablation of disease with minimal local or systemic adverse effects.

Intralesional PV‐10 for the treatment of in‐transit melanoma metastases—Results of a prospective, non‐randomized, single center study

“…PV‐10 causes direct tumor lysis, promotes selective lymphocyte‐mediated tumor destruction and is associated with a quantifiable local and systemic anti‐tumor response, including a T‐cell regulated abscopal effect in untreated lesions . PV‐10 has been investigated both as a single agent and in combination therapy with radiotherapy …”

A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

“…Table summarizes the key data for each modality and presents the pooled results including the weighted ORR and meta‐analysis data. Assessed studies included: randomized controlled trials, nonrandomized phase I and II comparative and noncomparative studies, and prospective or retrospective case series (NHMRC levels II–IV evidence; Tables S2‐S9) . Only two therapies: amputation and topical imiquimod, were suitable for formal meta‐analysis ( I 2 value ≤ 40%).…”

“…Thus, a key advantage of PV‐10 appears to be the favorable side effect profile and cost compared with IL‐2 and as an independent agent appears to have no negative impact on quality of life following treatment . These agents can also be used within the outpatient setting and can be combined with radiotherapy and imiquimod with synergism . These therapies are particularly useful for polymetastatic disease and nodular or bulky metastases that are otherwise inaccessible or would require significant surgical reconstruction.…”

Patients with in‐transit melanoma metastases have comparable survival outcomes following isolated limb infusion or intralesional PV‐10—A propensity score matched, single center study

“…12 A phase II study of PV-10 in 80 patients with metastatic melanoma reported a local complete response (CR) rate in injected target lesions of 26% with extended periods of local control (mean progression-free survival [PFS] 8.0 months). 14,15 Separately, both treatments have been reported to produced durable responses; however, a prospective study directly comparing long-term outcomes has not yet been performed. 14,15 Separately, both treatments have been reported to produced durable responses; however, a prospective study directly comparing long-term outcomes has not yet been performed.…”

“…This is relevant because studies have demonstrated that patients with a lower burden of disease experience improved response rates and PFS with treatment 14,15,26. Propensity score matching offers a pragmatic alternative to evaluate the relative treatment effect when conducting a larger adequately powered study is not feasible.There are several limitations to the current study.…”