Transcript:Ezra Cohen, MD: The CheckMate-141 study was a phase lll trial comparing nivolumab to the standard-of-care in patients whose cancers had progressed on platinum. Now, that really meant 2 cohorts: patients who had platinum in the locally advanced setting and who had evidence of progressive disease within 6 months of receiving platinum in that setting or patients who had recurrent metastatic disease who had a platinum-containing regimen and then who progressed. In a sense, we’re talking about patients, where some of them had first-line recurrent metastatic disease who had just come off locally advanced therapy and then some of them who were treated in the second line recurrent metastatic disease. What’s interesting is that the efficacy appeared to be very similar when we compared those groups. So, we’ll talk about them really as one.

These patients were enrolled in a 2:1 ratio to either receive nivolumab or the standard-of-care. Standard of care consisted of investigator choice of either methotrexate, docetaxel, or cetuximab, which are quite reasonable choices in this setting. The control arm of investigator choice faired exactly as we would expect it to: single-agent response rates, a 1-year survival of 17%, a median progression-free survival of about 2 months. That’s exactly what we’d expect from methotrexate, docetaxel, or cetuximab in patients with recurring metastatic disease.

What was really encouraging and heartening was to see how well nivolumab did in this trial. So, first of all, there was a 13% response rate and, most importantly, a 1-year overall survival of 36% compared to 17% with standard therapy. And so, now, really nivolumab is standard of care for patients who have recurrent metastatic head and neck cancer, whose cancers have progressed on a platinum-containing regimen. And not only that, but the efficacy came with a very favorable toxicity profile of 13% grade 3 or 4 serious adverse events.

Nabil F. Saba, MD: CheckMate-141, I believe, is a game changer in the treatment of recurrent and metastatic disease. This is, so far, the only phase III trial that has compared a single-agent checkpoint PD-1 inhibitor to investigators’ choice chemotherapy in a phase III randomized setting.

Prior to this trial, there was really no standard-of-care for patients who had recurrent or metastatic disease and if they failed platinum-based therapy. And the treatment choice was left up to the physicians to decide as far as what chemotherapy agent to use. But this is not the case since CheckMate-141 has been completed and reported. As you well know, the 1-year survival in the investigator’s choice arm was about 16.6%, whereas in the nivolumab arm, it was 36%. So, it was a significant improvement compared to different agents that are considered investigator’s choice agents for treatment of this disease.

I believe this trial has clearly resulted in a new standard for this heavily pretreated patient population and this patient population that has a very poor prognosis. Not only has it resulted in a new standard-of-care, it has also opened the door to investigate this agent in the concurrent setting, in the definitive treatment setting, the curative setting, and the early stage setting, and trials are already on their way to look at these possibilities in these different patient groups.

The important thing about it as well is that it seems to show that nivolumab is also preserving quality of life for patients who desperately need improvement and survival, but who also desperately need preservation of quality of life at this stage of their disease. So, from that standpoint, I think it’s also making a major difference.

So, my personal experience with using nivolumab does not differ very much from what the trial CheckMate-141 has reported and from what the pembrolizumab data show in KEYNOTE-012 and KEYNOTE-055. These drugs are overall very well tolerated. These drugs can produce fatigue in about 20% of patients when they receive them, but overall, however, patients tolerate them well. There are, however, the rare severe toxicities that may happen occasionally to patients, and those focus around the problems of immune, immune-related toxicities—whether it is endocrine-related or whether it’s gastrointestinal-related, or liver toxicities—but overall, I think these drugs are fairly well tolerated.

As far as the response rates to these drugs, as expected, they may produce deep and early responses in a small proportion of patients, but I think the vast majority of patients will basically have stable disease over a long period of time. And more importantly, as indicated, their quality of life seems to be fairly well preserved when they receive these drugs.

Transcript Edited for Clarity