Article Type
Changed
Tue, 06/25/2024 - 11:05

The US Food and Drug Administration (FDA) has granted accelerated approval to adagrasib (Krazati, Mirati Therapeutics) with cetuximab for certain patients with KRAS G12C–mutated colorectal cancer (CRC).

More specifically, the highly selective and potent small-molecule KRAS G12C inhibitor is now indicated for patients with locally advanced or metastatic KRAS G12C–mutated CRC — as determined by an FDA-approved test — who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and, if eligible, a vascular endothelial growth factor inhibitor, according to an FDA press release.

The agent is the first KRAS inhibitor approved for CRC. Adagrasib was previously granted accelerated approval for KRAS G12C–mutated non–small cell lung cancer, based on findings from the KRYSTAL-12 trial.

The CRC approval was based on findings from the KRYSTAL-1 multicenter, single-arm expansion cohort trial, which reported an overall response rate of 34% among 94 enrolled patients. 

All responses were partial responses, and the median duration of response was 5.8 months, with 31% of responding patients experiencing a duration of response of at least 6 months.

Patients received 600 mg of adagrasib twice daily plus cetuximab administered in either a biweekly 500 mg/m2 dose or an initial dose of 400 mg/m2 followed by weekly doses of 250 mg/m2. Those who discontinued adagrasib also had to discontinue cetuximab, but adagrasib could be continued if cetuximab was discontinued.

The recommended adagrasib dose is 600 mg given orally twice daily until disease progression or unacceptable toxicity, according to the prescribing information

Adverse reactions occurring in at least 20% of treated patients included rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

“Patients with KRAS G12C–mutated colorectal cancer have historically faced poor prognoses and remain in need of additional treatment options,” Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, stated earlier this year in a press release announcing the FDA’s decision to accept the drug application for priority review.

“Although KRAS had previously been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce the potential benefit of adagrasib for these specific patients,” Dr. Kopetz said in the statement from Bristol Myers Squibb, which acquired Mirati Therapeutics in 2023.

A version of this article first appeared on Medscape.com.

Publications
Topics
Sections

The US Food and Drug Administration (FDA) has granted accelerated approval to adagrasib (Krazati, Mirati Therapeutics) with cetuximab for certain patients with KRAS G12C–mutated colorectal cancer (CRC).

More specifically, the highly selective and potent small-molecule KRAS G12C inhibitor is now indicated for patients with locally advanced or metastatic KRAS G12C–mutated CRC — as determined by an FDA-approved test — who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and, if eligible, a vascular endothelial growth factor inhibitor, according to an FDA press release.

The agent is the first KRAS inhibitor approved for CRC. Adagrasib was previously granted accelerated approval for KRAS G12C–mutated non–small cell lung cancer, based on findings from the KRYSTAL-12 trial.

The CRC approval was based on findings from the KRYSTAL-1 multicenter, single-arm expansion cohort trial, which reported an overall response rate of 34% among 94 enrolled patients. 

All responses were partial responses, and the median duration of response was 5.8 months, with 31% of responding patients experiencing a duration of response of at least 6 months.

Patients received 600 mg of adagrasib twice daily plus cetuximab administered in either a biweekly 500 mg/m2 dose or an initial dose of 400 mg/m2 followed by weekly doses of 250 mg/m2. Those who discontinued adagrasib also had to discontinue cetuximab, but adagrasib could be continued if cetuximab was discontinued.

The recommended adagrasib dose is 600 mg given orally twice daily until disease progression or unacceptable toxicity, according to the prescribing information

Adverse reactions occurring in at least 20% of treated patients included rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

“Patients with KRAS G12C–mutated colorectal cancer have historically faced poor prognoses and remain in need of additional treatment options,” Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, stated earlier this year in a press release announcing the FDA’s decision to accept the drug application for priority review.

“Although KRAS had previously been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce the potential benefit of adagrasib for these specific patients,” Dr. Kopetz said in the statement from Bristol Myers Squibb, which acquired Mirati Therapeutics in 2023.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval to adagrasib (Krazati, Mirati Therapeutics) with cetuximab for certain patients with KRAS G12C–mutated colorectal cancer (CRC).

More specifically, the highly selective and potent small-molecule KRAS G12C inhibitor is now indicated for patients with locally advanced or metastatic KRAS G12C–mutated CRC — as determined by an FDA-approved test — who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and, if eligible, a vascular endothelial growth factor inhibitor, according to an FDA press release.

The agent is the first KRAS inhibitor approved for CRC. Adagrasib was previously granted accelerated approval for KRAS G12C–mutated non–small cell lung cancer, based on findings from the KRYSTAL-12 trial.

The CRC approval was based on findings from the KRYSTAL-1 multicenter, single-arm expansion cohort trial, which reported an overall response rate of 34% among 94 enrolled patients. 

All responses were partial responses, and the median duration of response was 5.8 months, with 31% of responding patients experiencing a duration of response of at least 6 months.

Patients received 600 mg of adagrasib twice daily plus cetuximab administered in either a biweekly 500 mg/m2 dose or an initial dose of 400 mg/m2 followed by weekly doses of 250 mg/m2. Those who discontinued adagrasib also had to discontinue cetuximab, but adagrasib could be continued if cetuximab was discontinued.

The recommended adagrasib dose is 600 mg given orally twice daily until disease progression or unacceptable toxicity, according to the prescribing information

Adverse reactions occurring in at least 20% of treated patients included rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

“Patients with KRAS G12C–mutated colorectal cancer have historically faced poor prognoses and remain in need of additional treatment options,” Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, stated earlier this year in a press release announcing the FDA’s decision to accept the drug application for priority review.

“Although KRAS had previously been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce the potential benefit of adagrasib for these specific patients,” Dr. Kopetz said in the statement from Bristol Myers Squibb, which acquired Mirati Therapeutics in 2023.

A version of this article first appeared on Medscape.com.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article