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Dr. Paz-Ares: 
This is CME on ReachMD, and I am Dr. Luis Paz-Ares, and today I will provide a brief overview of emerging practice-changing directions in non-small cell lung cancer within the perioperative and locally advanced settings. And indeed, I will particularly discuss the CheckMate 77T and the LAURA trial. And as you know, both indications had recently been approved by the FDA.

Starting by the CheckMate 77T trial, that was a randomized trial in the perioperative setting, so where patients with resectable stage IIA to IIIB in non-small cell lung cancer without EGFR or ALK rearrangement were randomized to receive 4 courses of chemotherapy plus placebo, control arm, or 4 courses of nivo plus chemotherapy then surgery in both treatment arms, and then those patients on the nivo arm continued with nivolumab for a year.

We have now substantial data suggesting that the primary endpoint of the trial was met with a clear decrease in the relapse rate and improvement in EFS for the nivolumab arm with a hazard ratio of 0.58, and that was actually affecting all the relevant subgroup of patients included in this very trial. Importantly, there was also some increase in the rate of pathological CR: 5% in the control arm compared to 25% in the experimental arm. And also was an increase in the major pathological response, 12% as compared to 35%.

So overall, those data are somehow consistent with data from other perioperative trials such as those on the KEYNOTE-671 trial, the AEGEAN, and some other trials that are worthy in this context.

Concerning to the LAURA trial, that is also a very relevant trial that had been performed in stage III patients with unresectable disease that was treated with chemoradiation. In any case, those patients should have had an EGFR mutation and were randomized after chemoradiation if they didn’t progress to receive osimertinib at the standard dose of 80 mg/day as compared to placebo.

Remember that the randomization ratio was 2:1, and the treatment actually impacted on the PFS on those patients with a substantial reduction on the risk of relapse with a hazard ratio of 0.16. And indeed, there was a clear decrease in the number of patients having distal metastases as well as also lack of progression when treated with osimertinib. And I really like to point it out here that a sub-analysis showed that the benefit was true for those patients that had been staged with PET scan as well as for those patients that did not have a staging in PET scan. And importantly, we’re looking at the time of relapse; it was clear, a decrease in the rate of relapse, not only local but also in distance sites, as we have mentioned. And importantly, there was a clear decrease in the incidence of CNS progression of those patients treated with osimertinib.

So taking all together those data, I think you may have tomorrow in your clinic some novel opportunities for those patients with locally advanced disease. If they have an EGFR mutation and are not candidates for surgery, those patients may be treated with chemoradiation and are really good candidates for osimertinib after chemoradiation if there is no progression.

For those patients that do have wild-type disease and are in a stage II or III, those may be ideal candidates to receive perioperative therapy with a number of possibilities. And among those, you may proceed into the future the CheckMate 77T type of protocol using chemotherapy plus nivolumab in the neoadjuvant setting, followed by nivolumab after surgery.

Well, all my time is up, and I hope you found this overview somehow useful. And thank you very much for listening.

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