ESMO 2019 News - Episode 5
Omid Hamid, MD, director of Research and Immuno-Oncology at The Angeles Clinic, discusses exciting immunotherapy data presented at the 2019 ESMO Congress.
Two-year follow-up data from a phase II trial (NCT02211131) evaluating neoadjuvant talimogene laherparepvec (T-VEC; Imlygic) in patients with resectable melanoma demonstrated an improvement in 2-year relapse-free survival (RFS; HR, 0.75) and overall survival (OS; HR, 0.49) with T-VEC versus surgery alone. Although the drug is approved for use as a single agent in the treatment of patients with locally advanced, unresectable melanoma, it is also being evaluated in combination with checkpoint inhibitors, says Hamid.
In the advanced setting, adjuvant therapy with nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) was evaluated in patients with stage IV melanoma with no evidence of disease in the phase II IMMUNED trial (NCT02523313). At a median follow-up of 28.4 months, there was a significant improvement in RFS with nivolumab alone versus placebo (HR, 0.56; 95% CI, 0.36-0.88) and with the combination versus placebo (HR, 0.23; 95% CI, 0.13-0.41).
These data, taken collectively with the results of the phase III CheckMate-238 and CheckMate-915 trials, will help inform future adjuvant combinations, says Hamid. Notably, 3-year findings from the CheckMate-238 trial demonstrated a superior RFS with adjuvant nivolumab versus ipilimumab in patients with resected stage III/IV disease (HR, 0.68; P < .0001), demonstrating a sustained benefit with PD-1 inhibition, says Hamid. Additionally, patients who had high tumor mutational burden and interferon gamma signature expression derived the greatest RFS benefit in both arms, indicating potential predictive value.
Superior activity was also reported in the 5-year OS analysis of the phase III CheckMate-067 trial with nivolumab alone (95% CI, 39-50) and in combination with ipilimumab (95% CI, 46-57) versus ipilimumab alone (95% CI, 22-31) in patients with advanced disease. These results confirm that PD-1 inhibition, either as monotherapy or in combination, should be used as frontline therapy in patients with unresectable or metastatic melanoma, says Hamid. Moreover, these data have set a standard for future drug development with PD-1 inhibition.
Although checkpoint inhibitors were the focus of the 2019 ESMO Congress in melanoma, a lot of work is being done to develop additional ways to manipulate the microbiome with oncolytic and adoptive T-cell therapies, and understand predictive as well as prognostic markers of response, such as circulating tumor cells and gene signatures, concludes Hamid.