Elaine Shum, MD, an assistant professor in the Department of Medicine at NYU Grossman School of Medicine, discusses emerging targeted therapies in 

-mutant non–small cell lung cancer (NSCLC).

A growing area of research is aimed at understanding resistance mechanisms that develop following progression on osimertinib (Tagrisso) in patients with 

-mutant NSCLC, explains Shum. Although these efforts are largely ongoing, the field hopes to establish a standard of care for patients.

For example, trials are under way evaluating various combinations of MET inhibitors plus osimertinib to try to overcome these resistance mechanisms, Shum says. 

Additionally, the investigational agent JNJ-6372 is being evaluated in patients with metastatic NSCLC who harbor 

 exon 20 insertion mutations, continues Shum. 

Other research efforts seek to understand why patients may develop 

 amplifications and C797S resistance mutations after osimertinib, Shum concludes. 

Videos

Elaine Shum, MD, discusses emerging targeted therapies in EGFR-mutant non–small cell lung cancer.  



Dr. Shum on Emerging Targeted Therapies in EGFR-Mutant NSCLC 

Elaine Shum, MD, an assistant professor in the Department of Medicine at NYU Grossman School of Medicine, discusses consulting patients with non–small cell lung cancer (NSCLC) on the use of osimertinib (Tagrisso).

The primary end point of the phase 3 ADAURA trial was looking at patients with stage II and III NSCLC, as well as those with stage IB disease, says Shum. An impressive hazard ratio for disease-free survival of 0.17 was observed in that group of patients, says Shum. This trial should be discussed with patients who have had resected lung cancer with an 

 mutation, according to Shum. For patients with stage II or III disease, it's definitely an option that can be pursued, says Shum.

For those with stage IB lung cancer, adjuvant chemotherapy is an option, although there is no set standard as to who receives it and who does not. In the clinic, having a discussion with the patient about whether or not to use osimertinib for 3 years for stage IB resected NSCLC is needed, concludes Shum.

Elaine Shum, MD, discusses consulting patients with non-small cell lung cancer on the use of osimertinib.

Dr. Shum on Patient Consultation of Osimertinib in NSCLC

Elaine Shum, MD, medical oncologist, NYU Langone’s Perlmutter Cancer Center, discusses the use of dacomitinib (Vizimpro) in the treatment of patients with 

-positive non—small cell lung cancer (NSCLC).

The second-generation EGFR TKI had very impressive data in the ARCHER 1050 study, Shum says, but the toxicity profile of the drug may be reason for concern. With dacomitinib, there is much stronger toxicity than what is typically observed with this class of drugs, especially when compared with osimertinib (Tagrisso), the frontline standard of care. Shum notes that personally, she would not consider using dacomitinib in the frontline due to toxicity alone. However, as more is understood about sequencing EGFR TKIs, dacomitinib could have a potential role in later lines of therapy.

In September 2018, the FDA approved dacomitinib as a frontline treatment option for patients with metastatic NSCLC who harbor 

 exon 19 deletion or exon 21 L858R substitution mutations. The approval was based on positive data from the phase III ARCHER 1050 trial, which showed a 40% reduction in the risk of disease progression or death compared with the first-generation EGFR TKI gefitinib (Iressa).

Elaine Shum, MD, medical oncologist, NYU Langone’s Perlmutter Cancer Center, discusses the use of dacomitinib in the treatment of patients with EGFR-positive non–small cell lung cancer.

Dr. Shum Discusses Dacomitinib in EGFR+ NSCLC

Elaine Shum, MD, medical oncologist, NYU Langone’s Perlmutter Cancer Center, discusses mechanisms of resistance in patients with oncogene-driven non—small cell lung cancer (NSCLC).

Based on data from the phase III FLAURA and ALEX studies, osimertinib (Tagrisso) and alectinib (Alecensa) have become the recommended frontline treatments for patients with 

-positive NSCLC, respectively. Physicians are still learning why tumors develop mechanisms of resistance, says Shum. Although there is no substantial insight into why this occurs, there is reason to believe that these targeted agents isolate a clone and allow for another clone to drive the disease undetected. Future studies involving more biopsies at the time of progression will hopefully shed more light on this issue, she adds.

For patients who have developed resistance to treatment, combination therapy with various TKIs may be a potential strategy, says Shum, although toxicity may become an issue. Additionally, some anecdotal studies have shown improved outcomes with an EGFR inhibitor and MET inhibitor in 

Elaine Shum, MD, medical oncologist, NYU Langone’s Perlmutter Cancer Center, discusses mechanisms of resistance in patients with oncogene-driven non–small cell lung cancer (NSCLC).

Elaine Shum, MD

Articles

Dr. Shum on Emerging Targeted Therapies in EGFR-Mutant NSCLC

Dr. Shum on Patient Consultation of Osimertinib in NSCLC

Dr. Shum Discusses Dacomitinib in EGFR+ NSCLC

Dr. Shum on Mechanisms of Resistance in Oncogene-Driven NSCLC