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BTOG 2021 | Immunotherapy for mesothelioma

Riyaz Shah, FRCP, PhD, Maidstone and Tunbridge Wells NHS Trust, Kent, UK, talks on the latest updates in the management and treatment of mesothelioma, highlighting the introduction of immunotherapies including immune checkpoint inhibitors such as nivolumab in the second line, and comparing results versus single-agent chemotherapy. Dr Shah also comments on data from the CheckMate 743 study (NCT02899299) of nivolumab and ipilimumab versus chemotherapy in the first line for patients with unresectable pleural mesothelioma. This interview took place during the 19th British Thoracic Oncology Group (BTOG) Annual Conference 2021.

Transcript (edited for clarity)

In terms of reviewing where we are in mesothelioma right now, from a BTOG perspective, the main thing that’s changed since the last BTOG is the introduction of immunotherapy into the management of this disease. We have an increasing, ever increasing body of evidence around the activity of checkpoint inhibitors in mesothelioma.

The two key things are that we’ve got multiple studies now in the subsequent-line setting, both Phase II and Phase III studies, showing that immunotherapy has activity...

In terms of reviewing where we are in mesothelioma right now, from a BTOG perspective, the main thing that’s changed since the last BTOG is the introduction of immunotherapy into the management of this disease. We have an increasing, ever increasing body of evidence around the activity of checkpoint inhibitors in mesothelioma.

The two key things are that we’ve got multiple studies now in the subsequent-line setting, both Phase II and Phase III studies, showing that immunotherapy has activity. It seems to have higher response rates than single-agent chemotherapy. It doesn’t seem to be more effective than single-agent chemotherapy, but it probably has less toxicity associated with it than single-agent chemotherapy.

So we have a role for second-line immunotherapy in mesothelioma, and I think the thing that’s changed since BTOG 2019 is that, because of the pandemic, we’ve been allowed access to nivolumab. So, through NHS COVID- NHS England COVID criteria, nivolumab was approved in both peritoneal and pleural mesothelioma, but only second-line – so it can’t be given third-line or beyond – only second-line in eligible patients.

The other thing that I was very much reflecting on is the more recent data on first-line immunotherapy. We now have a randomized Phase III trial, called the CheckMate 743 study, that compared doublet immunotherapy, nivolumab and ipilimumab, versus chemotherapy. It’s a large study, it’s a proper registration trial, and it pretty comprehensively demonstrates superior activity for immunotherapy, immunotherapy combinations.

The thing that’s important is it is, it is a new development. It’s a paradigm shift in the management of mesothelioma, because now we’re talking about omitting chemotherapy altogether in the first-line setting and just giving patients immunotherapy. But that is associated with the toxicity burden. So, there’s quite a significant burden of additional toxicity with this immunotherapy doublet that you can see in the trial data. And so, I think it’s a treatment that is certainly active and eligible patients should get it, but it’s a select group of eligible patients who have the appropriate fitness and robustness to receive that treatment.

The key thing about nivolumab and ipilimumab is it’s actually available through an Early Access to Medicines Scheme. So, there’s a scheme available run by BMS. There is a Blueteq form on the NHS England portal that needs completing, and then you need to complete some demographics into a trial platform called Medidata Rave. And essentially, as long as your trust approve it, you should be able to give nivolumab and ipilimumab to your patient. Slight difference in the NHS approval to what is in the published study in the NHS, it’s flat-dose nivolumab every three weeks, which actually makes sense for the patients. They’re only coming once every three weeks. They’re having ipilimumab six weekly and nivolumab flat-dose three weekly, so quite a straightforward regimen.

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Disclosures

Riyaz Shah, FRCP, PhD, discloses links to Boehringer Ingelheim, AstraZeneca, Roche, BMS, MSD, Pfizer, Lilly, Novartis, Takeda and Bayer.

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