Mary Jo J. Fidler, MD, an associate professor in the Department of Internal Medicine, Division of Hematology, Oncology and Cell Therapy at Rush Medical College, Rush University Medical Center, discusses the potential for novel agents in

 exon 20–mutated non–small cell lung cancer (NSCLC).

Encouraging signals have been observed with novel agents like mobocertinib (formerly TAK-788), when used in this patient population, despite toxicity challenges, Fidler says. However, there is optimism that progress will be made with EGFR inhibitors for this patient population, Fidler adds.

To accomplish more with these agents, it is important that the associated toxicity is effectively managed, Fidler says. More impact may be achieved by designing newer agents, schedules, or combinations for use in patients with 

 exon 20–mutant NSCLC, Fidler concludes.

Videos

Mary Jo J. Fidler, MD, discusses the potential for novel agents in EGFR exon 20–mutated non–small cell lung cancer.

Dr. Fidler on Balancing Benefit of Novel Agents in EGFR Exon 20–Mutant NSCLC With Toxicities 

Mary J. Fidler, MD, associate professor, Rush University Medical Center, discusses the utility of dacomitinib (Vizimpro) in patients with 

Dacomitinib is a second-generation irreversible EGFR TKI that has shown superior progression-free survival and overall survival (OS) compared with a first-generation agent; however, the agent is a little more toxic, says Fidler. Approximately two-thirds of patients in the phase III ARCHER 1050 trial required dose reductions. In a follow-up analysis, investigators showed that patients who were able to maintain the full dose of dacomitinib had less blood levels, suggesting a relationship between tolerability and metabolism. Notably, dose reductions were not associated with inferior outcomes, adds Fidler. 

Since dacomitinib is not designed to target T790M, it could be used up front. If patients develop an 

 T790M mutation, they could receive osimertinib (Tagrisso) in the second-line setting. However, according to data from the phase III FLAURA trial, the median OS of osimertinib in the frontline setting was 38.6 months versus 31.8 months with erlotinib (Tarceva) or gefitinib (Iressa). Although approximately 30% of patients in both arms were not able to receive second-line therapy, it has become the preferred frontline therapy. However, the optimal role of dacomitinib has yet to fully defined, concludes Fidler.

Mary J. Fidler, MD, discusses the utility of dacomitinib (Vizimpro) in patients with EGFR-mutant non–small cell lung cancer.

Dr. Fidler on the Utility of Dacomitinib in EGFR-Mutant NSCLC

Mary J. Fidler, MD, associate professor, Rush University Medical Center, discusses overall survival (OS) data of the phase III FLAURA trial evaluating the use of frontline osimertinib (Tagrisso) in 

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

The FLAURA trial was unique because it included patients with brain metastases, explains Fidler. The trial randomized patients with 

-mutant NSCLC to receive third-generation TKI osimertinib versus either of the first-generation TKIs erlotinib (Tarceva) or gefitinib (Iressa).

Initial results of the FLAURA trial showed that frontline osimertinib reduced the risk of disease progression or death by 54% compared with erlotinib or gefitinib in this patient population. The 3-year OS data, presented at the 2019 ESMO Congress, showed that patients treated with osimertinib has longer OS at 38.6 months (95% CI, 34.5-41.8) versus 31.8 months (95% CI, 26.6-36.0) for patients treated with erlotinib or gefitinib (HR, 0.799; 95% CI, 0.647-0.997; 

Although a positive step forward, more research is needed in order to change lung cancer into a chronic illness, Fidler concludes.

Mary J. Fidler, MD, discusses overall survival data of the phase III FLAURA trial looking at frontline osimertinib in EGFR-mutant non–small cell lung cancer.

Dr. Fidler on the FLAURA Trial in EGFR-Mutant NSCLC

Mary J. Fidler, MD, associate professor, Rush University Medical Center, discusses the results of the phase III RELAY trial in treatment-naïve patients with 

The RELAY trial is studying the potential benefit of adding an angiogenic inhibitor to frontline TKI therapy, explains Fidler. Some signals were seen when using bevacizumab (Avastin) in a similar study in the United States, but the RELAY trial in Japan using erlotinib (Tarceva) had more positive responses. This is because erlotinib is a monoclonal antibody targeting the receptor rather than the circulating VEGF protein, says Fidler.

The RELAY trial in Japan randomized patients to receive erlotinib plus ramucirumab or placebo. Results presented at the 2019 ESMO Congress showed that the erlotinib plus ramucirumab combination had a median progression-free survival of 19.4 months versus 12.4 months for erlotinib plus placebo, resulting in a 41% reduction in the risk of disease progression or death (HR, 0.59; 95% CI, 0.46-0.79; 

 ≤.0001) at a median follow-up of 20.7 months. Despite these data, erlotinib is not the most-used drug in United States prescribing patterns for treatment-naïve patients with EGFR-mutant NSCLC, concludes Fidler.

Mary J. Fidler, MD, discusses the results of the phase III RELAY trial in treatment-naïve patients with EGFR-mutant non–small cell lung cancer.

Dr. Fidler on RELAY Trial Results in EGFR+ NSCLC

Mary J. Fidler, MD, associate professor, Rush University Medical Center, discusses progression-free survival (PFS) and overall survival (OS) in patients with stage IV, nonsquamous, non—small cell lung cancer (NSCLC) treated with first-line pemetrexed (Alimta) and platinum followed by pemetrexed maintenance.

Patients in the study had stage IV nonsquamous NSCLC and received at least one cycle of pemetrexed and platinum-based chemotherapy between May 2010 and November 2013. The PFS rate at years 1, 2, 3, 4, and 5 were 33%, 14%, 7.5%, 4%, and 3%. OS from years 1 to 5 was 54.5%, 36%, 21%, 14%, and 11%, respectively. A lower baseline neutrophil, as assessed by lymphocyte ratio, hemoglobin, and albumin were associated with better PFS.

The study found that patients with better PFS and OS had favorable baseline prognostic indicators; therefore, this patient subset might benefit from the recently approved regimen of frontline pembrolizumab (Keytruda) with pemetrexed and platinum-based chemotherapy.

Mary J. Fidler, MD, associate professor, Rush University Medical Center, discusses progression-free survival (PFS) and overall survival (OS) in patients with stage IV, nonsquamous, non–small cell lung cancer patients (NSCLC) treated with first-line pemetrexed and platinum followed by pemetrexed maintenance.

Mary J. Fidler, MD

Articles

Dr. Fidler on Balancing Benefit of Novel Agents in EGFR Exon 20–Mutant NSCLC With Toxicities

Dr. Fidler on the Utility of Dacomitinib in EGFR-Mutant NSCLC

Dr. Fidler on the FLAURA Trial in EGFR-Mutant NSCLC

Dr. Fidler on RELAY Trial Results in EGFR+ NSCLC

Dr. Fidler on Novel Chemotherapy Strategies in Nonsquamous NSCLC