Progression-free survival (PFS) in unresectable melanoma patients (pts) treated with talimogene laherparepvec (T-VEC) versus granulocyte macrophage colony-stimulating factor (GM-CSF) in OPTiM.

Abstract

9524 Background: T-VEC is a modified oncolytic herpes virus designed as an intralesional therapy for unresectable advanced melanoma. OPTiM was a randomized, phase 3 trial that showed improved durable response rate (DRR) with T-VEC vs GM-CSF in pts with unresectable melanoma with regional or distant metastases (16.3% vs 2.1%, p < 0.001). Treatment benefit of T-VEC on DRR and overall survival (OS) was greater in stage IIIB-IVM1a vs IVM1b-IVM1c melanoma. This is the first report of PFS for T-VEC vs GM-CSF. Methods: OPTiM included pts ≥18 yrs with unresectable stage IIIB-IV melanoma; ≥1 injectable cutaneous, subcutaneous (SC), or nodal lesion; ECOG ≤1; LDH ≤1.5 ULN; ≤3 visceral metastases (excluding lung) with none > 3 cm. Pts were randomized 2:1 to receive intralesional T-VEC or SC GM-CSF. The primary endpoint was DRR (partial or complete response continuously for ≥6 mo starting within 12 mo) and reported previously. In this post hoc analysis, PFS was evaluated overall and by disease stage. Results: This analysis included 436 pts: 295 (68%) T-VEC, 141 (32%) GM-CSF; 57% men; 63 yr median age; 57% stage IIIB-IVM1a, 43% stage IVM1b-IVM1c. In the intention to treat set, T-VEC significantly improved PFS (HR: 0.68, 95% CI: 0.54, 0.85, unstratified log-rank p < 0.001). In stage IIIB-IVM1a, PFS favored the T-VEC arm vs the GM-CSF arm (HR: 0.60, 95% CI: 0.44, 0.80, unstratified log-rank p < 0.001). No treatment difference was seen in stage IVM1b-IVM1c (HR: 0.81, 95% CI: 0.57, 1.15, unstratified log-rank p = 0.199). Overall, the 12 mo PFS rate for T-VEC was 14.4% (95% CI: 10.5, 18.8) and GM -CSF was 4.6% (95% CI: 1.6, 10.2). In stage IIIB-IVM1a, the 12 mo PFS rate for T-VEC was 19.9% (95% CI: 14.0, 26.6) and GM-CSF was 3.2% (95% CI: 0.6, 9.9). In stage IVM1b-IVM1c, the 12 mo PFS rate for T-VEC was 7.4% (95% CI: 3.5, 13.2) and GM-CSF was 8.0% (95% CI: 1.9, 20.1). Conclusions: T-VEC demonstrated an improvement in PFS vs GM-CSF, driven primarily by pts with stage IIIB-IVM1a melanoma. This is consistent with previous data showing more pronounced OS benefit with T-VEC and greater efficacy with other immunotherapies in early metastatic disease. Clinical trial information: NCT00769704.