Jonathan W. Riess, MD, on EGFR-Mutated Non–Small Cell Lung Cancer: What’s Next?

2023 ASCO Annual Meeting


Jonathan W. Riess, MD, of the University of California, Davis Comprehensive Cancer Center, explores the findings of three important clinical trials in lung cancer treatment: whether to incorporate immune checkpoint inhibitors into the treatment of EGFR-mutated lung cancer, the importance of central nervous system activity in EGFR-mutant lung cancer, and new therapies for disease with EGFR exon 20 insertion.


Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Jonathan W. Riess, MD: At this ASCO 2023 annual meeting, I'm speaking on EGFR-mutated non-small cell lung cancer: What's next? And I'll be discussing three important abstracts that will be presented at the oral session for metastatic non-small cell lung cancer. The first abstract is KEYNOTE 789, which is adding pembrolizumab immunotherapy to platinum pemetrexed based chemotherapy. It's a clinical trial that randomizes patients with advanced EGFR-mutated non-small cell lung cancer who've progressed on prior EGFR tyrosine kinase inhibitor to either chemotherapy or chemotherapy plus pembrolizumab. And this is an important study because patients with EGFR-mutated non-small cell lung cancer were excluded from many of the pivotal chemo-immunotherapy clinical trials in the past, because we think of these tumors as being less responsive to single agent immunotherapy. And in this study there was no clear progression-free survival or overall survival benefit with the addition of pembrolizumab to platinum pemetrexed based chemotherapy. This study highlights the importance of better selecting patients with EGFR-mutated non-small cell lung cancer for that small population that might benefit from immunotherapy or immune checkpoint inhibitor combinations, as well as, other potential factors that may potentiate the immune response. Within this study, it looked like patients whose tumors had positive PD-L1 expression might do slightly better, but once again, no overall survival or progression-free survival benefit was shown. So it is not clear and it does not show that immunotherapy added to chemotherapy provides any benefit to these patients. There are further studies looking at the combination of immunotherapy with anti-angiogenesis agents in combination with chemotherapy, and there may be some potentiation of immune activity with that anti-angiogenesis immunotherapy ICI interaction. But we still have yet to see an overall survival benefit from studies already conducted, and we eagerly await the results of future studies. For the second abstract I will be discussing, it's zorifertinib in EGFR-mutant non-small cell lung cancer. This trial, conducted in Asia, randomized patients to a highly CNS penetrant, EGFR TKI zorifertinib versus first-generation EGFR TKI erlotinib or gefitinib. And in this study for patients with treatment-naive EGFR-mutant non-small cell lung cancer with active untreated asymptomatic brain metastases, zorifertinib improved progression-free survival compared to erlotinib or gefitinib and also had an increased PFS in terms of intracranial progression. Now, osimertinib is also an EGFR tyrosine kinase inhibitor with high CNS penetration and has shown a progression-free survival and overall survival benefit compared to gefitinib or erlotinib. But this drug may not be available at all places in the world, although it's the standard of care in the United States. And so, it's unclear right now if this will change the standard of care of the future because of osimertinib being used in the first-line setting in the United States and Europe in many parts of the world. The third abstract I'll be discussing is sunvozertinib and EGFR Exon 20 insertion non-small cell lung cancer. These are uncommon EGFR-mutations, yet important ones. They're the third most common EGFR activating mutation. About 10 to 12% of EGFR-mutated non-small cell lung cancer. And there's been a number of advances recently with the FDA approval of amivantamab and mobocertinib after progression on platinum-based chemotherapy. Sunvozertinib was studied in the WU-KONG6 study, which I will be discussing, and that showed, in patients who have had prior treatment for EGFR Exon 20 insertion non-small cell lung cancer, a response rate of 60.8%, which looks favorable in the context of other recently approved Exon 20 agents such as amivantamab and mobocertinib. Sunvozertinib has favorable activity with response rate of 60.8% in the WU-KONG6 trial. It also appears to have CNS activity, which is important and compares very favorably to current FDA approved agents amivantamab and mobocertinib. Some unanswered questions are the sequencing of Exon 20 agents, as well as, potential combinations strategies in the future, but this looks like to be an exciting drug that's being developed further.

Related Videos

Lung Cancer

Penelope Bradbury, MBChB, on Pleural Mesothelioma: New Results From the IND227 Trial of Cisplatin and Pemetrexed With or Without Pembrolizumab

Penelope Bradbury, MBChB, of Canada’s Princess Margaret Cancer Centre, discusses phase III findings showing that, in patients with treatment-naive unresectable pleural mesothelioma, cisplatin and pemetrexed with pembrolizumab improved median overall survival with acceptable tolerability (Abstract LBA8505).


Nirav N. Shah, MD, on DLBCL: New Data on Split-Dose R-CHOP for Older Patients

Nirav N. Shah, MD, of the Medical College of Wisconsin, discusses phase II results showing that split-dose R-CHOP offers older patients with diffuse large B-cell lymphoma (DLBCL) an equivalent dose intensity as R-CHOP-21 through a fractionated dosing schedule, improving tolerability. At the end of treatment for these older patients, a complete response rate of 71% was comparable to outcomes with R-CHOP in younger patients with the disease (Abstract 7554).


Tycel J. Phillips, MD, and Alex F. Herrera, MD, on Classical Hodgkin Lymphoma: New Data on Nivolumab, AVD, and Brentuximab Vedotin

Tycel J. Phillips, MD, and Alex F. Herrera, MD, both of the City of Hope National Medical Center, discuss results from the SWOG S1826 study, which showed that nivolumab and AVD (doxorubicin, vinblastine, and dacarbazine) improved progression-free survival vs brentuximab vedotin plus AVD in patients with advanced-stage classical Hodgkin lymphoma. Longer follow-up is needed to assess overall survival and patient-reported outcomes. This trial may be a key step toward harmonizing the pediatric and adult treatment of advanced-stage disease (LBA4).

Global Cancer Care

Paula Aristizabal, MD, MAS, on Surviving Childhood Leukemia Near the Border of the United States and Mexico

Paula Aristizabal, MD, MAS, of the University of California, San Diego, and Rady Children’s Hospital, talks about using a health systems strengthening approach to improve leukemia care and survival in a public Mexican hospital in the region of the border between the United States and Mexico. The demonstrated increase in overall survival across a decade after implementation of the program seems to validate the use of such models, not only to improve clinical outcomes, but also to build sustainable hospital capacity, financially and organizationally (Abstract 1502).

Skin Cancer

Allison Betof Warner, MD, PhD, and Adnan Khattak, PhD, MBBS, on High-Risk Resected Melanoma: Survival Results With mRNA-4157 and Pembrolizumab in KEYNOTE-942

Allison Betof Warner, MD, PhD, of Stanford University Medical Center, and Adnan Khattak, MBBS, FRACP, PhD, of Australia’s Hollywood Private Hospital & Edith Cowan University, discuss the use of the mRNA-4157 vaccine in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma, which prolonged distant metastasis–free survival compared with pembrolizumab alone. These results provide further evidence that a personalized neoantigen approach is potentially beneficial (Abstract LBA9503).