Dr Mark Kris discusses neoadjuvant approaches for patients non-small cell lung cancer with oncogenic drivers for which there are effective targeted therapies.
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-- TRANSCRIPT --
Hello. It's Mark Kris from Memorial Sloan Kettering. I'm speaking today about the use of neoadjuvant approaches in patients with non-small cell lung cancer who have an oncogenic driver in their tumors, and particularly an oncogenic driver for which we have an effective targeted therapy.
For many years, I've been an advocate of treating patients with oncogenic drivers in the perioperative setting with targeted therapies. I think that approach has been supported by the lack of substantial benefit from checkpoint inhibitors in patients with targets, both EGFR and ALK.
Frankly, with the approval of neoadjuvant therapy with the checkpoint inhibitor nivolumab and chemotherapy, they specifically say that you should not give this regimen in patients who have EGFR and ALK rearrangements. It must be true because I hear it on television.
However, the trials that have been proposed - and I've been involved in creating many of these trials - have generally given single-agent checkpoint inhibitors. There's a regulatory reason for doing that. In thinking about what would be the optimal approach, I don't think that I can recommend that at this point.
Please remember that the goal in these patients is not to lengthen a time free of cancer, per se, and not to lengthen their length of life, per se. It is to cure the patient. When that is the goal, we clearly need to use every little edge, every modality that we have, to improve the chance of curing the patient. I think the data are pretty clear. It's clearest for EGFR that chemotherapy needs to be part of the mix with the TKI.
What do I base that on? First, please remember that in one of the original trials that put gefitinib on the map, it was compared to chemotherapy. In the cohort of patients that had an EGFR mutation, their response to chemotherapy was double that of patients who did not have an EGFR mutation. There's something inherent about the presence of the EGFR mutation that imparts a greater sensitivity to chemotherapy.
I think all of you have seen, but largely ignored, the two clinical trials, one from India and one from Japan, showing that gefitinib with chemotherapy prolonged disease-free survival and also prolonged overall survival. Those data came out in 2019 but have not been widely adopted.
I think we all heard a few months ago about giving osimertinib with chemotherapy. The combination, again, in stage IV disease, gives people an improvement in survival of about 9 months. At least in my mind, in fit patients who can accept the extra side effects and the drugs can be added safely, that's the thing to do.
We've seen the data from the ADAURA trial. Again, this is not exactly comparable because there are people with EGFR mutations who received chemotherapy followed by osimertinib, but those patients who received osimertinib after their chemotherapy had better survival. Clearly, here in the perioperative setting, the chemotherapy makes a difference.
I think we have all seen the data from ALINA. That is not a trial where chemotherapy and alectinib were given. It was just alectinib. I point that out again to show the role of these agents in the perioperative setting.
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