Durable response to T-VEC, GM-CSF linked to longer OS

Source: Healio.com/hematology-oncology, April 2015

NEW YORK — Patients with unresected stage IIIB, stage IIIc or stage IV melanoma who achieved durable response to either talimogene laherparepvec or granulocyte-macrophage colony–stimulating factor demonstrated longer OS than those who did not achieve a durable response, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

n the randomized phase 3 OPTiM trial, researchers compared talimogene laherparepvec (T-VEC, Amgen) — a systemically active oncolytic immunotherapy derived from herpes simplex virus type-1 — with GM-CSF in patients with unresectable stage IIIb, stage IIIc or stage IV melanoma.

All patients were aged 18 years or older and had injectable cutaneous, subcutaneous or nodal lesions. All patients had up to three visceral lesions but none were larger than 3 cm.

The intention-to-treat analysis included 496 patients (median age, 63 years; 57% men). Of these, 295 (68%) received intralesional T-VEC at an initial dose of ?4 mL x 106 pfu/mL. After 3 weeks, the dose was changed to ?4 mL x 108 pfu/mL every 2 weeks.

The other 141 (32%) patients received subcutaneous GM-CSF administered in doses of 125 µg/m2 daily for 14 days every 4 weeks.

The primary OS analysis showed T-VEC was associated with longer median OS (23.3 months vs. 18.9 months; HR = 0.79; 95 % CI, 0.62-1).

In the current analysis, Howard L. Kaufman, MD, FACS, chief surgical officer, associate director for clinical science and a surgical oncologist with Rutgers Cancer Institute of New Jersey, and colleagues assessed the association between durable response and OS in both arms.

The investigators compared OS for all patients who were alive — at 9 months (n = 335), 12 months (n = 304) and 18 months (n = 236 months) post-randomization. Of these patients, 22 achieved durable response by 9 months, 36 achieved durable response by 12 months and 50 patients achieved durable response by 18 months.

Results showed a considerably reduced risk for death among patients who achieved durable response by 9 months (HR = 0.07; 95% CI, 0.01-0.48), 12 months (HR = 0.05; 95% CI, 0.01-0.33) and 18 months (HR = 0.11; 95% CI, 0.03-0.44).

A Cox proportional hazards model showed a consistent association between survival and achievement of durable response (HR = 0.08; 95% CI, 0.03-0.26).

“These analyses suggest a strong association between achieving a durable response and a lower risk of death,” Kaufman and colleagues wrote. “Although the study design does not allow a definitive causal relationship to be established, an assumption that achieving a durable response would extend OS is supported here. Further explorations of durable response as a OS surrogate in patients with melanoma receiving immunotherapy are warranted.” – by Cameron Kelsall

For more information:

Kaufman HL, et al. Association between durable response (DR) and overall survival (OS) in patients with unresected stage IIIB/C/IV melanoma with talimogene laherparepvec or GM-CSF in the randomized phase 3 OPTiM trial. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 10-11, 2015; New York.

Disclosure: Kaufman reports research funding from Bristol-Myers Squibb; consultant roles with and honoraria or other expenses from Alkermes, Amgen, EMD Serono, Merck, Prometheus and Sanofi; and a speakers bureau role with Merck. See the full study for a list of all other researchers’ relevant financial disclosures.