The Case for Adding Chemotherapy in Fit Patients With EGFR-Mutant Lung Cancer

Mark G. Kris, MD


October 02, 2023

This transcript has been edited for clarity.

Hello. This is Mark Kris, from Memorial Sloan Kettering. I recently returned from Singapore and the World Conference on Lung Cancer. I think there was general agreement that the biggest piece of news to come out of that conference was the presentation by Pasi Jänne of the trial comparing osimertinib alone to osimertinib plus carboplatin and pemetrexed chemotherapy in patients with newly diagnosed EGFR-mutant lung cancers.

What's the background to this question? In 2019, there were two presentations and two publications on adding gefitinib to chemotherapy or adding chemotherapy to gefitinib. Both publications in the Journal of Clinical Oncology showed an improvement in both progression-free and overall survival, and interestingly, that improvement was 8 and 9 months, respectively.

There is every reason to think that adding chemotherapy to osimertinib would give that same degree of improvement of approximately 9 months. Lo and behold, in Dr Jänne's presentation, adding chemotherapy to osimertinib gave an improvement in progression-free survival of 9 months. I should add that both of those earlier trials with gefitinib showed that there was an improvement not only in disease-free survival but also overall survival, for individuals who are interested in that statistic as well.

There were a couple other interesting observations in that trial. One is that patients who had chemotherapy at the time of diagnosis had an 11-month improvement in progression-free survival. That is counterintuitive because people have this idea in their head that chemotherapy doesn't really work well with brain metastases, but clearly it does, and it did here.

The last thing this trial showed was that there was essentially no difference between patients with L858R and exon 19 EGFR mutations. There is usually a significant difference in both progression-free and overall survival comparing those two different mutation types; however, in this case, adding chemotherapy to osimertinib eliminated that difference as well. There is every reason to suggest the addition of chemotherapy.

Years ago, I attended a lecture by Zosia Piotrowska, from Massachusetts General Hospital. She is one of the brightest people in the world when it comes to this disease. Somebody asked her during the question-and-answer session, "If you could do something today to improve the outcome in people with EGFR-mutant cancer at the time of diagnosis, what would you do?" She said, "I'd give chemotherapy."

I wholeheartedly agree. Many of you who know me know I've been recommending chemotherapy with osimertinib ever since those original publications with gefitinib, and I continue to do that. I would, frankly, recommend it to any patient at this point who is fit enough to receive chemotherapy. Obviously, it adds another degree of difficulty to the administration of the treatment, and I do believe that needs to be talked through. Not every patient chooses to do it, and that's to be understood. I do think it needs to be brought up.

I'd urge you to consider recommending chemotherapy with osimertinib in every single fit patient at the time of diagnosis. I think it deserves to be brought up as an option and as the best thing we have now to improve progression-free survival.

Please remember, from the patient's standpoint, that progression-free survival is absolutely key, particularly in an illness like EGFR-mutant lung cancer that we do not cure. Having disease progression, particularly after years of good disease control, is an extreme hardship. Even if it's not a symptomatic progression, it's still very difficult for patients, and frankly, for most patients who I see, it's a more difficult time than the time of the original diagnosis.

We have a new treatment that improves progression-free survival, which is very important to patients. We know we can safely deliver carboplatin and pemetrexed, and I urge you to discuss it with every patient, and, in my opinion, to recommend it to every patient who is fit.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

Follow Medscape on Facebook, X (formerly known as Twitter), Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.