Promising Treatment Combinations in EGFR+ NSCLC

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Sai-Hong Ignatius Ou, MD, PhD: Another promising approach in the treatment of EGFR-mutant lung cancer is to use a combination of chemotherapy with an EGFR TKI [tyrosine kinase inhibitor]. I am actually a proponent for combining chemotherapy with an EGFR TKI. People have to understand that EGFR-mutant lung cancer is not just 1 mutation, it’s very heterogeneous. Patients who have a p53 mutation do poorly compared to patients who don’t have a p53 mutation, for example. Chemotherapy should be able to decrease all of the resistant clones regardless of what the genetic makeup is. At this year’s ASCO [American Society of Clinical Oncology] Annual Meeting, it was suggested that the combination of carboplatin-pemetrexed plus gefitinib was better than gefitinib alone. The improvement in overall survival is a testament that this combination should be explored and should not be ignored.

Also, in difference to ALK-positive lung cancer, where the single-agent TKI response rate is in this 80% range, the response rate to an EGFR TKI is about 70%. So, there’s still some room for improvement. The fact is, the combination of chemotherapy with a first-generation EGFR TKI can improve overall survival compared to a first-generation EGFR TKI alone. I think we should explore this with the combination of osimertinib and chemotherapy, potentially with the use of Avastin [bevacizumab]. In the erlotinib-bevacizumab combination study, there is improved progression-free survival compared to erlotinib alone. So, there is additional benefit with the use of bevacizumab to an EGFR TKI.

I would ideally like to see the combination of an EGFR TKI, chemotherapy, with a platinum pemetrexed-based chemotherapy, and an antiangiogenic agent get explored. Somebody has to do the randomized trial. An ideal regimen would be osimertinib, carboplatin-pemetrexed, and bevacizumab versus osimertinib alone. It would be interesting to see if we can further improve the progression-free survival, or even overall survival, in EGFR-mutant lung cancer.

Transcript Edited for Clarity