Bob T. Li, MD, PhD, MPH, medical oncologist, physician ambassador to China and Asia-Pacific, Bobst International Center, co-director, Thoracic Liquid Biopsy Program, chief scientific officer, MSK Direct, Memorial Sloan Kettering Cancer Center, discusses the limitations of the phase 3 IMpower010 trial (NCT02486718) in resected stage IB to IIIA non–small cell lung cancer (NSCLC).

The results of the IMpower010 study demonstrated a statistically significant improvement in disease-free survival with adjuvant atezolizumab (Tecentriq) vs best supportive care in patients with stage II to IIA NSCLC. On August 3, 2021, the FDA granted priority review to a supplemental biologics license application for atezolizumab after surgery and platinum-based chemotherapy in patients with NSCLC whose tumors have a PD-L1 expression of 1% or higher per an FDA-approved test. The application is supported by the results of the IMpower010 trial. 

Although the potential approval is welcome in the treatment of patients with resected NSCLC, further investigation into the biomarker analysis of the study beyond PD-L1 expression is warranted, Li says. It is important to evaluate the blood plasma of patients to determine who was cured with surgery and who is likely to relapse. In the latter group, aggressive adjuvant treatment may be indicated, Li adds.

Moreover, more precise clinical trials with available technologies that evaluate the likelihood of cure vs relapse are needed to determine whether patients should receive more intensive adjuvant therapy, Li concludes.

This activity is funded in part by Daiichi Sankyo. Content independently produced by 

Videos

Bob T. Li, MD, PhD, MPH, discusses the limitations of the phase 3 IMpower010 trial in resected stage IB to IIIA non–small cell lung cancer.



Dr. Li on the Limitations of the IMpower010 Trial in Resected Stage IB-IIIA NSCLC 

Bob T. Li, MD, PhD, MPH, medical oncologist, physician ambassador to China and Asia-Pacific, Bobst International Center, co-director, Thoracic Liquid Biopsy Program, chief scientific officer, MSK Direct, Memorial Sloan Kettering Cancer Center, discusses the results of the phase 2 DESTINY-Lung01 trial (NCT03505710) in HER2-positive metastatic non–small cell lung cancer (NSCLC).

Findings from the DESTINY-Lung01 trial, which were presented during the 

, demonstrated robust and durable anticancer activity with the antibody-drug conjugate (ADC) fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with previously treated HER2-mutated NSCLC. Moreover, efficacy was consistently observed across patient subgroups, including in those with central nervous system metastases. 

Drug-related interstitial lung disease (ILD) and pneumonitis were generally low-grade and manageable; however, early detection and management is important to prevent serious ILD and pneumonitis among patients. 

Although cytotoxic agents are often difficult to tolerate, ADCs like trastuzumab deruxtecan, which link a cytotoxic chemotherapy payload to a trastuzumab (Herceptin) antibody, appear to be well tolerated and elicit clinically meaningful activity in patients with HER2-positive NSCLC. Moreover, these data represent an encouraging step forward in the treatment of this patient population, Li concludes.

Bob T. Li, MD, PhD, MPH, discusses the results of the phase 2 DESTINY-Lung01 trial in HER2-positive metastatic non–small cell lung cancer.



Dr. Li on the Results of the DESTINY-Lung01 Trial in HER2+ Metastatic NSCLC 

Bob T. Li, MD, PhD, MPH, co-director of the Thoracic Liquid Biopsy Program and physician ambassador to China and Asia-Pacific, Bobst International Center at Memorial Sloan Kettering Cancer Center, discusses the efficacy of sotorasib (AMG 510) in patients with 

 G12C–mutated advanced non-small cell lung cancer (NSCLC), as demonstrated in phase 2 cohort results of the phase 2 CodeBreaK 100 trial (NCT03600883).

In this trial, investigators doubled down on inhibiting 

 G12C with sotorasib, says Li. The trial accrued 126 patients with advanced-stage, refractory 

 G12C–mutant NSCLC, Li says. Each patient received the full dose of oral sotorasib at 960 mg once daily.

Results showed an overall response rate of 37.1%, a disease control rate of 80.6%, and tumor shrinkage in approximately 80% of patients, Li notes. The median progression-free survival was 6.8 months with the agent, while the median duration of response was 10 months, which validates data from the phase 1 trial and confirms that this drug is active in this patient population, Li concludes.

Bob T. Li, MD, PhD, MPH, discusses the efficacy of sotorasib in patients with KRAS G12C–mutated advanced non-small cell lung cancer, as demonstrated in phase 2 cohort results of the phase 2 CodeBreaK 100 trial.

Dr. Li on the Efficacy of Sotorasib in KRAS+ Advanced NSCLC

Bob T. Li, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the application of liquid biopsies in lung cancer.

Liquid biopsies are already a reality in lung cancer, says Li. They’re now used readily in the detection of oncogenic drivers that could lead to targeted therapy options for patients. They can also be used to detect resistance mechanisms that may then guide subsequent treatment for patients.

Liquid biopsies have a lot of potential beyond their current use, explains Li, in terms of treatment monitoring for molecular response, detection of and screening for early-stage disease, as well as in providing evidence of minimal residual disease. The technology has the potential to extend the reach of precision medicine for patients with early-stage disease who have undergone standard therapies, adds Li. Moreover, it has the potential to guide neoadjuvant therapy, extended adjuvant therapy, indicate a curative state, as well as indicate whether chemotherapy is necessary. These are all future potential applications, states Li, but the technology still needs to be developed further to make this possible.

Bob T. Li, MD, MPH

Articles

Dr. Li on the Limitations of the IMpower010 Trial in Resected Stage IB-IIIA NSCLC

Dr. Li on the Results of the DESTINY-Lung01 Trial in HER2+ Metastatic NSCLC

Dr. Li on the Efficacy of Sotorasib in KRAS+ Advanced NSCLC

Dr. Li on the Application of Liquid Biopsies in Lung Cancer