- The concept of intralesional therapy:
- For locoregional in-transit disease (or more broadly speaking for other accessible metastases) in melanoma is not new
- A potential advantage of such a strategy:
- Is that a direct targeted approach may be associated with limited systemic toxicity:
- While at the same time promoting a favorable local immune response and potentially direct cytotoxic activity
- Is that a direct targeted approach may be associated with limited systemic toxicity:
- Historically, this approach has been considered for patients with:
- Unresectable, multiple, or locally advanced locoregional disease:
- As well as patients with accessible M1a disease
- Unresectable, multiple, or locally advanced locoregional disease:
- T-VEC (talimogene laherparepvec):
- Is the only currently FDA-approved intralesional agent
- It leverages the role of:
- Granulocyte macrophage colony stimulating (GM-CSF) injection and its theoretical contribution to antitumor immunity
- The agent is an attenuated oncolytic herpes simplex virus:
- That has been modified to express the GM-CSF gene and is also capable of selective replication in tumor cells
- The antitumor effect is thought to be due to a combination of:
- A direct oncolysis from the viral infection and lytic replication
- As well as the induction of a systemic immune response
- In a phase III trial reported by Andtbacka et al:
- 436 patients were enrolled and randomized to T-VEC or GM-CSF (control)
- All patients had unresectable, injectable stage III or IV melanoma with a limited visceral disease burden
- T-VEC was administered by intralesional injections once every 2 weeks, while in the other arm GM-CSF was administered subcutaneously daily for 14 days in each 28-day cycle
- The durable (defined as ≥ 6 months) response rate, the primary objective of the trial:
- Was significantly increased in patients receiving T-VEC (16.3% vs. 2.1%), as was the overall response rate (26.4% vs. 5.7%)
- Some antitumor effects were observed in approximately one-third of uninjected lesions and in slightly more than 10% of visceral sites
- OS was not significantly different among the arms of the trial:
- However, in subset analysis there appeared to be a survival advantage in patients with stage III or IV (M1a) disease:
- 4-year OS 32% vs. 21%, HR 0.57, 95% CI 0.40 to 0.80
- However, in subset analysis there appeared to be a survival advantage in patients with stage III or IV (M1a) disease:
- Treatment with T-VEC was well tolerated:
- Commonly reported adverse events included fatigue, chills, pyrexia, and other systemic flu-like symptoms
- Based on these positive clinical results, in 2015, T-VEC became the first intralesional therapy approved by the FDA for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery
- Efforts have been made to build upon the success of ILI and intralesional therapy (T-VEC in particular)
- Ariyan et al. examined the safety and efficacy of combining ipilimumab with ILI in patients with in-transit disease:
- After administering combination therapy to 26 patients, they observed response rates of 85% at 3 months (62% CR) and progression-free survival (PFS) at 1 year of 57%
- A recent positive phase II trial comparing T-VEC followed by surgery versus surgery alone in stage IIIB to IV(M1a) melanoma:
- Demonstrated an improvement in 2-year recurrence-free survival from 16.5% among 74 patients in the surgery alone arm to 29.5% in the 76 patients included in the T-VEC followed by surgery arm
Rodrigo Arrangoiz MS, MD, FACS, FSSO 