Wade T. Iams, MD, assistant professor of medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, discusses the impact of adagrasib (Krazati) on the treatment of patients with 

 G12C-mutant non–small cell lung cancer (NSCLC) in the second line, as well as its integration into clinical practice.

The introduction of KRAS G12C inhibitors to this treatment armamentarium has significantly improved outcomes for patients with 

 G12C-mutant NSCLC. Adagrasib has emerged as a key therapeutic option for this patient population following its 

accelerated approval by the FDA for adult patients with 

 G12C–mutated locally advanced or metastatic NSCLC

 who received at least 1 prior systemic therapy, Iams states.

This regulatory decision, which was made on December 12, 2022, was based on data from the phase 1/2 KRYSTAL-1 trial (NCT03785249), showing that the agent produced an objective response rate of 43% in this population and a median duration of response of 8.5 months.

Prior to the approval of KRAS G12C inhibitors, patients with this mutation had limited second– or later-line treatment choices, Iams says. Commonly utilized approaches included chemotherapy regimens such as docetaxel with or without ramucirumab (Cyramza) or gemcitabine; however, these options are often associated with challenging toxicities and less favorable outcomes, he explains.

Adagrasib has been well-received in the clinical setting, Iams reports. It exhibits a manageable toxicity profile, and healthcare providers can employ a dose-reduction strategy to effectively address any adverse events that may arise during treatment, he adds. This enhances the drug's tolerability and allows more patients to benefit from its therapeutic effects, Iams says.

As a result, the approval and utilization of adagrasib and other KRAS G12C inhibitors have expanded the available treatment choices for patients with 

 G12C-mutant NSCLC, Iams states. These inhibitors have demonstrated their potential to be more effective than traditional chemotherapy options, ultimately enhancing the quality of life for patients and improving outcomes, Iams concludes.

Videos

Wade T. Iams, MD, discusses the impact of adagrasib on the treatment of patients with KRAS G12C-mutant NSCLC in the second line, as well as its integration into clinical practice.

Dr Iams on the Impact of Adagrasib on Patient Outcomes in KRAS G12C–Mutant NSCLC  

Wade T. Iams, MD, assistant professor of medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, discusses the impact of the phase 3 FLAURA2 trial (NCT04035486) in patients with 

-mutant non–small cell lung cancer (NSCLC) , highlighting the notable improvements in progression-free survival (PFS) that this approach elicits.

Investigators presented updated data from the trial during the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer

 Updated data from the study showed that osimertinib (Tagrisso) plus platinum-based chemotherapy and pemetrexed produced a statistically significant and clinically meaningful improvement in PFS when compared withosimertinib monotherapy in patients with advanced, 

Notably median PFS increased from 16.7 months with osimertinib alone to 25.5 months with the combinationin this patient group, Iams adds. The 12-month PFS rates were 80% with the combination and 66%, with single-agent osimertinib. The 24-month PFS rates were 57% vs 41%, respectively.

Iams emphasizes that this improvement in PFS closely aligns with previous hypotheses regarding the survival data, which solidify the use of osimertinib in the adjuvant setting. Moreover, survival data from FLAURA2 indicate that the addition of platinum-doublet chemotherapy to initial treatment regimens should be the standard approach for patients with metastatic 

In summary, the data from FLAURA2 further demonstrate the potential benefits associated with the upfront use of combination therapy in metastatic 

Wade T. Iams, MD, discusses the impact of the phase 3 FLAURA2 trial in patients with EGFR-mutant non–small cell lung cancer, highlighting the notable improvements in progression-free survival that the approach elicits.

Dr Iams on the Effect of the FLAURA2 Trial in EGFR-Mutant NSCLC

Martin Dietrich, MD, PhD, and Wade Thomas Iams, MD, review the value of TROP2 as a target in patients with NSCLC.

Exploring TROP2 Expression in Patients with NSCLC

Experts review data on treatment with HER3-directed agents in NSCLC for patients with EGFR mutations.

Targeting HER3 in EGFR-Mutant NSCLC

Dr Wade Thomas Iams explains how trastuzumab deruxtecan became the standard-of-care for HER2-mutated non-small cell lung cancer.

HER2-Directed Agents in NSCLC

Martin Dietrich, MD, PhD, details the molecular target CEACAM5 and its use in the treatment of patients with non-small cell lung cancer.

Targeting CEACAM5 in Patients with Non-Small Cell Lung Cancer

Drs Martin Dietrich and Wade Thomas Iams discuss the differences between the targets, payloads, and linker technologies of the antibody drug conjugates in development for lung cancer.

ADCs in Development for the Treatment of Lung Cancer

Wade Thomas Iams, MD, provides an overview of antibody drug conjugates in the treatment of patients with lung cancer, including challenges and impact on clinical practice.

Wade Thomas Iams, MD

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