EGFR tyrosine kinase inhibitors (TKIs) have been integrated into early treatment for non-small cell lung cancer (NSCLC) patients with EGFR mutations. Upon disease progression, some clinicians suggest that continued TKI use in conjunction with chemotherapy is the optimal strategy for patient care. Others contend there is a lack of conclusive evidence to recommend this approach, particularly with the added toxicity and financial burden this treatment can place on patients.
During the 2023 Targeted Therapies of Lung Cancer Meeting in Santa Monica, California, two experts debated the pros and cons during “Session 1: Targeted Therapies—EGFR, HER2 and MET.” Registered attendees can view the session on-demand.
Balazs Halmos, MD, associate director for clinical science and chief of thoracic/head & neck oncology at Montefiore Einstein Cancer Center, New York, argued in favor of continued TKI use and Mark Socinski, MD, who is executive medical director of AdventHealth Cancer Institute, Orlando, questioned the evidence for TKI use with chemotherapy upon disease advancement.
In advocating for TKIs, Dr. Halmos cited research that demonstrated their multifaceted utility. He highlighted multiple studies that recommend continued TKI application for patients with oligoprogressive disease,1 MET amplification,2 and central nervous system disease.3 He also cited an ongoing frontline study4 measuring the benefit of chemotherapy with osimertinib versus chemotherapy plus placebo in patients with EGFR mutated advanced NSCLC. While this study is still in progress, and results are not expected until 2024, Dr. Halmos said he is confident they will support his argument.
“Osimertinib is really like chocolate if you think about it,” Dr. Halmos said. “It goes with everything: radiation, targeted therapy, and chemotherapy.”
Unconvinced, Dr. Socinski argued that there is not yet sufficient evidence to recommend TKIs after disease progression. He cited the absence of randomized trial data and pointed out that the National Comprehensive Cancer Network did not recommend this approach in its guidelines.
Dr. Socinski also said that the toxicity of TKIs in conjunction with chemotherapy made them an inconvenient solution for patients. While the toxicity of these treatments rarely exceeds moderate levels, Dr. Socinski cited a study that showed patients treated with gefitinib and chemotherapy experienced slightly higher rates of diarrhea, stomatitis, vomiting, and anemia than control group patients treated with chemotherapy and placebo.
“There are consequences of continuing this [treatment], even though there might be potential benefits,” Dr. Socinski said.
He also asserted that the financial burden of TKI and chemotherapy on patients outweighed the current potential benefits. According to patient survey data presented by Dr. Socinski, 70% of patients report financial hardship from cancer-related expenses.6 Among that sample, 86% characterized the financial burden as moderate or severe. In the survey cited by Dr. Socinski, prescription medications were identified as the second most common out-of-pocket medical expense for patients.
“The financial burden bears consideration by all of us who care for patients,” Dr. Socinski said.
- 1. Weickhardt AJ, Scheier B, Burke JM, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol. 2012;7(12):1807-1814. doi:10.1097/JTO.0b013e3182745948
- 2. Sequist LV, Han JY, Ahn MJ, et al. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study. Lancet Oncol. 2020;21(3):373-386. doi:10.1016/S1470-2045(19)30785-5
- 3. White MN, Piotrowska Z, Stirling K, et al. Combining Osimertinib With Chemotherapy in EGFR-Mutant NSCLC at Progression. Clin Lung Cancer. 2021;22(3):201-209. doi:10.1016/j.cllc.2021.01.010
- 4. Sequist LV, Peled N, Tufman A, et al. P47.11 COMPEL: Chemotherapy With/Without Osimertinib in Patients With EGFRm Advanced NSCLC and Progression on First-Line Osimertinib. J Thorac Oncol. 2021; 16(10) https://doi.org/10.1016/j.jtho.2021.08.504
- 5. Soria JC, Wu YL, Nakagawa K, et al. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol. 2015;16(8):990-998. doi:10.1016/S1470-2045(15)00121-7
- 6. Patient Survey: Financial Hardship Associated with Cancer