麻豆传媒

Three-year follow-up results from the phase III were presented at the , demonstrating that nivolumab (Opdivo) plus ipilimumab (Yervoy) in overall survival and additional efficacy measures as a first-line treatment for patients with metastatic non-small cell lung cancer.

In this exclusive 麻豆传媒 video, , a thoracic oncology specialist at City of Hope in Duarte, California, examines both sides of the key question: whether the immunotherapy combination offers a real benefit versus the treatments already in place.

Following is a transcript of his remarks:

One of the issues around ASCO 2020 in terms of advanced non-small cell has been the question of whether there should be a role for nivolumab and ipilimumab as a combination immunotherapy approach for patients with advanced non-small cell lung cancer whose cancer does not harbor a driver mutation. We have standard chemotherapy combined with pembrolizumab for both squamous and non-squamous non-small cell lung cancer. And we also have, particularly for patients with high tumor PDL-1 expression, pembrolizumab as monotherapy and a recent approval for atezolizumab. So we might question whether there is a role, or should be a role, for an immunotherapy combination.

Now, Checkmate 227 has been presented several times in the last few years, and it looked at nivolumab and ipilimumab or another arm that was chemo with nivolumab for some patients, versus chemotherapy. And particularly the nivo-ipi combination has been shown to improve survival compared to chemotherapy.

More recently, at ASCO 2020, we also saw results for , a trial that looked at giving nivolumab and ipilimumab for four cycles with the nivolumab, and then continuing with nivo, and combining that with two cycles of initial chemotherapy, compared to a platinum doublet chemotherapy that was histology appropriate, but without immunotherapy as first line.

That trial also showed a significant improvement in survival and has been approved by the FDA. So we have more options than we can possibly use.

And I would say the question now is should there be a place for an approach with nivolumab and ipilimumab, either alone or combined with a couple of cycles of chemotherapy for patients whose cancer we really want to make sure we get control of, and it doesn't get away from us before immunotherapy works.

To be clear, I would say there's no best answer to this. And many of us are debating this point of whether there is an incremental benefit to an immunotherapy combination versus what we already have in 2019, 2020, because the comparator of chemo alone that was beaten by nivo-ipi with or without chemo, is an old standard we don't really use anymore. But it arguably could be better for patients in terms of sustained responses. And many of my colleagues who have used a good amount of nivo-ipi in trials or off trial would say that some of their best responders and longest responses have been with that combination, but that's just anecdotal.

We don't really have a direct comparison in one trial. We just have cross-trial comparisons that don't really clearly tell us that nivo-ipi is a stronger, better option, but it is certainly an option. Others would say that it might be good to have a treatment option that is as aggressive as anything we might do, but still leaves a chemo doublet as an option to pursue, whereas if we do something like KEYNOTE-189 or KEYNOTE-407, standard platinum doublet combined with pembro, we've pretty much exhausted that chemo doublet option by the time a patient is progressing into second-line treatment.

That said, it's important to note that a chemo-free or a chemo-light option is not to say less toxic. Nivo and ipi in a combination has a pretty comparable toxicity intensity as any platinum doublet combination, even if the side effects are different.

In the end, I think it's really an issue of preference. And some patients may strongly prefer an option with little or no chemotherapy. Some physicians may favor an option that preserves a chemo doublet to be waiting in the wings upon progression. Other docs may say as a general tenet, we like to give our best treatments upfront. And if that's chemo immunotherapy, the way we have typically with a pembro combination, there is no clear need to change that.

So I think it's really a matter of preference. What we have now are more options.

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