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Expert Discusses Latest Findings With Nivolumab/Ipilimumab Combo in Melanoma

Laura Panjwani
Published: Friday, Apr 29, 2016

Patrick Ott, MD, PhD

Patrick Ott, MD, PhD

The combination of ipilimumab (Yervoy) and nivolumab (Opdivo) continues to show promise, with recent data demonstrating a 26% improvement in overall survival (OS) with the 2 drugs compared with ipilimumab alone for patients with advanced melanoma.

In a 2-year assessment of the phase II CheckMate-069 trial,1 which was recently presented at the 2016 AACR Annual Meeting, 142 treatment-naïve patients with unresectable stage III or metastatic stage IV melanoma were randomized to receive either the combination (n = 95) or ipilimumab plus placebo (n = 47) every 3 weeks for 4 doses followed by nivolumab or placebo every 2 weeks until disease progression or unacceptable toxicity.

In the overall treatment population, the 2-year OS rate was 64% with the combination compared with 54% for ipilimumab alone (HR, 0.74; 95% CI, 0.43-1.26). The median OS at 2 years in patients randomized to either the combination or monotherapy has not been reached.

The 2-year OS rate with nivolumab/ipilimumab was 69% compared with 53% for ipilimumab alone in patients with BRAF wild-type melanoma. The median OS among patients was not reached with the combination regimen and was 24.8 months with ipilimumab monotherapy (HR, 0.58; 95% CI, 0.31-1.08).

Previous findings from the CheckMate-067 study demonstrated a superior progression-free survival and overall response rate with the combination over the monotherapy.

The data make it clear that, for many patients, nivolumab/ipilimumab is the best option, says Patrick Ott, MD, PhD, clinical director, Melanoma Center, Center for Immuno-Oncology, physician, assistant professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute.

“I feel very strongly that the combination is the way to go,” Ott says. “The data says it all. Due to the potential durability with the combination, I think it is hard to argue that we could just start out with PD-1 monotherapy.”

Despite its benefits, there are still many questions that remain regarding the use of nivolumab/ipilimumab in advanced melanoma. In an interview with OncLive, Ott discusses toxicity management and patient selection considerations required with the combination, and its role in BRAF-mutant melanoma.

OncLive: How do you decide which patients should receive the combination therapy versus monotherapy?

Ott: We really consider everybody for the combination. Patients who have high comorbidities may not be candidates for the combination, but we have had 80-year-old patients who have received it; they have had great outcomes.

Therefore, I wouldn’t say, “Don’t try it with older people.” We do have some patients who don’t want it, but that is relatively rare. We also enroll patients in clinical trials where other combinations are explored, and it is certainly very reasonable to try that approach.

How much of a factor are toxicities in determining whether patients should receive the combination?

The toxicities with nivolumab/ipilimumab are a big problem; however, it’s often worth it for patients. Patients have a 20% higher chance of having a durable response for metastatic melanoma. That may mean that they have to spend a few weeks in the hospital or go on steroids for a few months and be OK. For most patients, the 20% improvement in chance is worth that. If you talk to patients who went through it and had good outcomes, they certainly think it’s worth it.

What questions remain to be answered regarding the use of nivolumab/ipilimumab in melanoma?

There is primary resistance and some patients also develop resistance to immunotherapies. Increasing the response from 40% to 60% is really remarkable, but there are still 40% of patients who don’t respond in the first place.

There are also patients who progress on the nivolumab/ipilimumab combination, but those numbers are very low so far. There is a lot of work to do to assess why that is—in terms of studying the immune infiltrates and biopsies and doing a comprehensive immune analysis.

What other immunotherapy combinations have potential in melanoma?

There is the PD-1 and IDO inhibitor combination that has been fairly successful. Ipilimumab plus T-VEC is also being investigated. Data were presented 2 years ago on 16 or 17 patients that showed fairly provocative response rates with that combination. There is now a larger study with 200 patients.

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Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Evolving Roles for Targeted Melanoma Therapies: Assessing Rapid Progress in the Field and Looking Toward Future CombinationsFeb 28, 20191.5
Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
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