Updates in Pharmacotherapy for Melanoma

Angie Amado, PharmD Candidate 2019; Sonia Amin Thomas (Sonia Patel), PharmD, BCOP


US Pharmacist. 2018;43(6):HS2-HS9. 

In This Article

Talimogene Laherparepvec

For patients in whom complete surgical excision to clear margins is not feasible, clinical trial treatment is the first-line recommendation. Other local, regional, or systemic therapies may be considered.[5] Patients with a limited number of in-transit metastases, particularly dermal lesions, which are not receptive to complete surgical excision, should be considered for intralesional local injections.[5] Intralesional injection of talimogene laherparepvec (T-VEC) is recommended by the NCCN as first-line therapy in patients with unresectable stage III in-transit disease based on improved durable response rate (DRR) and overall response rate (ORR) versus injection with granulocyte macrophage colony-stimulating factor (GM-CSF) alone.[5]

Intralesional injection of melanoma metastases with GM-CSF resulted in modest response rates or stable disease in several small clinical studies.[30–33] These and other studies led to the development of T-VEC, which uses a modified herpes simplex virus to induce tumor-cell lysis and deliver localized expression of GM-CSF to injected lesions.[34] In a recent phase III trial, selected patients with unresectable stage IIIB-IV melanoma were randomized to intralesional injection of T-VEC versus SC injection of GM-CSF.[35] Patients had at least one cutaneous, SC, or nodal lesion or aggregation of lesions greater than 10 mm in diameter, measurable disease, and limited distant metastatic disease. T-VEC produced clinically significant DRRs in injected tumors, as well as a bystander effect on some uninjected nonvisceral and visceral tumors.[36] At median followup of approximately 44 months, T-VEC patients had higher DRRs (16.3% vs. 2.1%, P <.001) and ORRs (26.4% vs. 5.7%, P <.001) than GM-CSF patients.[35] In subset analyses, the effect of T-VEC on response rate was greater in patients with lessadvanced disease. T-VEC patients with stage IIIB or IIIC disease had a DRR of 33% compared with 0% for GM-CSF patients; for patients with stage IV-M1a disease, the effect of T-VEC on DRR was smaller (16.0% vs. 2.3%). The effect of T-VEC on DRR was far greater in patients with previously untreated metastatic disease (23.9% vs. 0%) than in those with previously treated disease (9.6% vs. 5.6%). Common toxicities were fatigue, chills, pyrexia, nausea, flulike illness, injection-site pain, and vomiting; treatment-related grade 3–4 toxicities, which occurred in 11% of patients, included injection-site reactions (e.g., cellulitis, pain, peripheral edema) and systemic toxicities (fatigue, vomiting, and other flulike symptoms).[35]

If T-VEC is not available, intralesional injection with IL-2 is another option, as is injection with bacillus Calmette-Guérin or interferon.[5] These options are NCCN category 2B recommendations.