Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma

Abstract

Background: Cutaneous head and neck melanoma has poor outcomes and limited treatment options. In OPTiM, a phase 3 study in patients with unresectable stage IIIB/IIIC/IV melanoma, intralesional administration of the oncolytic virus talimogene laherparepvec improved durable response rate (DRR; continuous response ≥6 months) compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF).

Methods: Retrospective review of OPTiM identified patients with cutaneous head and neck melanoma given talimogene laherparepvec (n = 61) or GM-CSF (n = 26). Outcomes were compared between talimogene laherparepvec and GM-CSF treated patients with cutaneous head and neck melanoma.

Results: DRR was higher for talimogene laherparepvec-treated patients than for GM-CSF treated patients (36.1% vs 3.8%; p = .001). A total of 29.5% of patients had a complete response with talimogene laherparepvec versus 0% with GM-CSF. Among talimogene laherparepvec-treated patients with a response, the probability of still being in response after 12 months was 73%. Median overall survival (OS) was 25.2 months for GM-CSF and had not been reached with talimogene laherparepvec.

Conclusion: Treatment with talimogene laherparepvec was associated with improved response and survival compared with GM-CSF in patients with cutaneous head and neck melanoma. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1752-1758, 2016.

Keywords: cancer immunotherapy; cutaneous head and neck melanoma; oncolytic virus; talimogene laherparepvec.

Figure 1

(A) Representative images from a patient with melanoma of the scalp with metastasis to cervical lymph nodes and liver (stage IVM1c). The patient was diagnosed 2 years before enrollment in OPTiM and had 2 surgeries: one at diagnosis, and another 1 year after recurrence. Top row: injection sites shown in yellow arrows at baseline (left panel). Uninjected sites are shown with green dashed arrows. Black dots mark tumor lesions. Sites included 1 fluorodeoxyglucose (FDG)‐avid left upper level V cervical lymph node (center left panel) and 2 FDG‐avid liver lesions (center right and right panels). Middle row: injections were stopped after complete resolution of scalp lesions after cycle 2 (1 cycle = 2 injections of talimogene laherparepvec). Bottom row: Complete resolution of cervical and liver tumors was documented by FDG‐PET CT at cycle 7. Patient was in complete response until the end of the trial, duration of response (complete response) was approximately 17 months.

Figure 2

Representative images from a patient with stage IIIC disease randomized to talimogene laherparepvec who had a complete response. The patient was enrolled in the study with desmoplastic melanoma of the forehead with bilateral cervical fluorodeoxyglucose‐avid lymph nodes (left panel). Talimogene laherparepvec was injected only into the cutaneous lesion marked by the label (top row). At month 4, a partial response was reported and injection of talimogene laherparepvec was stopped. At cycle 6, a complete remission was reported that continued until the end of the study. Duration of response was 15.5 months. The patient was disease‐free at last follow‐up contact approximately 3 years after enrollment.

Figure 3

Duration of response for all patients with a response per endpoint assessment committee (EAC) was censored (marked by arrow) if at the last tumor assessment there was no evidence (per EAC) that the response had ended. Probability of being in response was estimated using the Kaplan–Meier method. Because only 1 patient in the granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) group had a response lasting >3 months, probability of being in response was not calculated for this group.

Figure 4

(A) Time to treatment failure per investigator assessment. (B) Overall survival. CI, confidence interval; GM‐CSF, granulocyte‐macrophage colony‐stimulating factor; IQR, interquartile range; NE, not estimable; OS, overall survival.