Collin Blakely, MD, PhD, assistant clinical professor, Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco (UCSF), UCSF Health, discusses a phase 2 trial evaluating the use of neoadjuvant osimertinib (Tagrisso) in patients with surgically resectable 

-mutated non-small cell lung cancer (NSCLC), findings from which were presented at the 2023 ASCO Annual Meeting.

EGFR inhibitors are effective in the metastatic setting for treating patients with 

-mutated lung cancer, which occurs in approximately 15% to 20% of lung adenocarcinoma cases, Blakely begins, adding that trials such as the phase 3 ADAURA trial (NCT02511106) have shown that adjuvant treatments also improve disease-free survival compared with placebo. The rationale for conducting further research into this topic is for investigators to best understand the possibility of moving EGFR inhibitors earlier in the treatment course, prior to surgery, Blakely explains.

Trials such as the phase 3 KEYNOTE-671 study (NCT03425643) have shown that neoadjuvant treatments for patients with NSCLC, specifically chemotherapy in combination with immunotherapy, generate event-free survival, major pathological response, and pathological complete response improvements compared with placebo. However, immunotherapy cannot be used in 

-mutated lung cancer because of its toxicity profile and lack of efficacy in this population, Blakely emphasizes. Therefore, investigators aimed to evaluate neoadjuvant treatment with osimertinib in patients with surgically resectable 

-mutated lung cancer, specifically including patients with 

 L858R– or exon 19 deletion–positive disease, he notes.

The primary end point of this study was major pathological response, which is now a well-accepted end point in a surgical neoadjuvant study, he expands. Major pathological response was defined as less than 10% viable cancer cells seen by the pathologist at surgery. Other studies have shown potential correlations between major pathological response and overall survival. Although this end point hasn't been thoroughly studied, it is a surrogate end point that many investigators are using in neoadjuvant trials, Blakely explains.

In this trial, the investigators hypothesized that osimertinib would elicit a high major pathological response rate, with the goal of a 50% major pathological response rate, he continues. However, in the 27 patients included in the trial, the major pathological response rate was 15%, Blakely concludes.

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Collin Blakely, MD, PhD, discusses a phase 2 trial evaluating the use of neoadjuvant osimertinib in patients with surgically resectable EGFR-mutated non-small cell lung cancer, findings from which were presented at the 2023 ASCO Annual Meeting.


Dr Blakely on the Rationale for Investigating Neoadjuvant Osimertinib in EGFR-Mutated NSCLC

Collin Blakely MD, PhD, associate professor of medicine, University of California, San Francisco (UCSF), medical oncologist, UCSF Health, discusses the design of an ongoing phase 2 trial (NCT03433469) examining osimertinib (Tagrisso) in resectable 

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

The non-randomized, multi-institution trial screened patients with stage I to IIIA NSCLC, Blakely explains. Patients who have 

 mutation or an exon 19 deletion, were eligible for enrollment, Blakely adds. Patients who met all screening criteria received 1 to 2 months of neoadjuvant osimertinib, followed by standard surgical resection, Blakely says.

The tissue was analyzed for major pathological response and patients were continuously followed after surgery to examine disease-free and overall survival, Blakely continued. In the adjuvant setting, patients could receive physician’s choice of standard therapy, such as chemotherapy or osimertinib, Blakely concludes.

Collin Blakely MD, PhD, discusses the design of an ongoing phase 2 trial examining osimertinib in resectable EGFR-mutant non–small cell lung cancer.

Dr. Blakely on the Design of a Trial Evaluating Osimertinib in Resectable EGFR-Mutant NSCLC 

Collin Blakely MD, PhD, associate professor of medicine, University of California, San Francisco (UCSF), medical oncologist, UCSF Health, discusses the rationale for utilizing osimertinib (Tagrisso) in resectable 

 mutations in NSCLC is an effective way to induce tumor shrinkage, Blakely says. Moreover, adjuvant osimertinib has been shown to extend disease-free survival in patients with 

-mutated disease. However, it is not known whether it is possible to utilize osimertinib in the neoadjuvant setting and obtain the same degree of tumor reduction and pathological response as in the adjuvant setting, Blakely explains.

Pathological response has been shown to correlate with overall survival; this concept served as the basis to evaluate neoadjuvant osimertinib in patients with early-stage NSCLC, Blakely concludes.

Collin Blakely MD, PhD, discusses the rationale for utilizing osimertinib in resectable EGFR-mutant non–small cell lung cancer.

Collin Blakely MD, PhD

Articles

Dr Blakely on the Rationale for Investigating Neoadjuvant Osimertinib in EGFR-Mutated NSCLC

Dr. Blakely on the Design of a Trial Evaluating Osimertinib in Resectable EGFR-Mutant NSCLC

Dr. Blakely on Utilizing Osimertinib in Resectable EGFR-Mutant NSCLC