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Non-small cell lung cancer (NSCLC) is characterized by various genetic alterations that drive its growth and progression. Fortunately, targeted therapies offer a more personalized and effective treatment approach by specifically targeting these molecular abnormalities.

Recent advancements in this area have significantly impacted the management of NSCLC, providing new hope for patients with specific mutations. So with that in mind, let's dive into the latest updates in targeted therapies for NSCLC, focusing on the key advancements and their relevance to improving patient care.

KRAS^G12C Inhibitors: Sotorasib, Adagrasib

An estimated 12.5 percent of patients with NSCLC have the KRAS^G12C mutation. Sotorasib, the first FDA-approved KRAS^G12C inhibitor, and adagrasib, the second, have demonstrated significant clinical benefits in patients with KRAS^G12C-mutated NSCLC.

This advancement has opened new avenues for the treatment of NSCLC, particularly for patients with this specific mutation who have received at least one prior systemic therapy. In fact, the most recent NCCN Practice Guidelines supports KRAS^G12C inhibitor use in this patient population with a Category 2A level of evidence.

However, there are some key differences between these two treatments that we need to be aware of, as outlined below in Table 1.

Table 1. KRAS^G12C Inhibitor Comparison

EGFR Exon 20 Inhibitors: Amivantamab and Mobocertinib

Amivantamab and mobocertinib have shown promising efficacy in patients with EGFR exon 20-mutated NSCLC. These mutations occur in up to 10 percent of patients, and they’re more common in people who have never smoked and in Asian people.

By the end of 2021, there were two FDA-approved EGFR exon 20 inhibitors; however, with the recent announcement of the voluntary withdrawal of mobocertinib, only amivantamab remains available. Details regarding these two agents appear in Table 2, and amid the recent announcement, other agents are being investigated to fulfill this unmet need.

Table 2. EGFR Exon 20 Inhibitor Comparison

As with other targeted therapies, resistance over time may develop. However, the uniqueness of the mechanism of action may aid in overcoming treatment resistance and provide sustained benefits when other options have been exhausted.

These and other advancements in targeted therapies for NSCLC have significantly improved the prognosis and treatment options available for patients with specific mutations. And these updates further highlight the importance of molecular profiling to maximize treatment efficacy and minimize toxicity.

References:

Le X, Elamin YY, Zhang J. New Actions on Actionable Mutations in Lung Cancers. Cancers (Basel). 2023;15(11). doi:10.3390/cancers15112917

Takeda. Takeda Provides Update on EXKIVITY® (mobocertinib). Published October 2, 2023. Accessed November 29, 2023. https://www.takeda.com/newsroom/newsreleases/2023/Takeda-Provides-Update-on-EXKIVITY-mobocertinib/ 

Exkivity (mobocertinib). Takeda Pharmaceuticals America, Inc.,. Published online September 2023.

RYBREVANT (amivantamab-vmjw). Package insert. Janssen Pharmaceutical Companies; . Published online May 2021.

Centers for Disease Control and Prevention. Lung Cancer Statistics. Published June 8, 2023. Accessed November 28, 2023. https://www.cdc.gov/cancer/lung/statistics/index.htm