In May 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval for sotorasib (LUMAKRAS^®/LUMYKRAS^®), an oral medication for the treatment of KRAS G12C-mutated cancers, at a daily dose of 960 milligrams (mg) based on phase I¹ and phase II² clinical trial data. However, research published from the phase III³ FDA-mandated dose-ranging response study, which compared a daily sotorasib dose of 960 mg with 240 mg, validated that patients would experience lower toxicity and adverse effects when the lower dose was administered.

Sotorasib is approved as a second line treatment for non-small-cell lung cancer (NSCLC), and is included in National Comprehensive Cancer Network (NCCN^®) guidelines.⁴ The guidelines also include sotorasib as a single agent in colon, rectal, ampullary, and pancreatic cancers,⁵ and small bowel adenocarcinoma.

New dose recommendations

The new recommended dosage is the result of an FDA phase III clinical trial that validated that patients would experience lower toxicity and adverse effects when a 240 mg daily dose was administered.

According to the phase III study:

• The pharmacokinetics are identical, and efficacy is maintained.
• There is no significant improvement in overall survival (13.0 months for 960 mg and 11.7 months for 240 mg).
• The progression free survival is the same.
• There is 36 percent versus 19 percent grade 3 toxicity, favoring the lower dose.

Patient benefits

For patients, the lower dose decreases unnecessary toxicity and reduces the risk from intense adverse effects of the medication. In turn, this leads to increased tolerance and adherence to the treatment regimen with a reduced negative impact on quality of life.

Prior authorization and dosage recommendations

BeginningMarch 1,when submitting a prior authorization on the EviCore by Evernorth^® (EviCore) portal for the KRAS G12C inhibitor sotorasib at:

• a dose of 240 mg, the request will follow the standard medical oncology prior authorization process. (There is no change.)
• a dose of 960 mg, the EviCore portal will produce a prompt, “Sotorasib at a dose of 960 mg a day is the requested dose. The data supports that a dose of 240 mg a day has similar pharmacokinetics, maintains efficacy, and decreases toxicity. Would you like to change the dose? (Yes or No)
  • If yes, the request will follow the standard medical oncology prior authorization process. (There is no change.)
  • If no, the request will be pended for a peer-to-peer discussion with an EviCore medical oncologist who will discuss the evidence to administer a lower dose and retain efficacy, and whether it is an option for the patient.

• If after the peer-to-peer discussion:
  • the request is changed from the daily dose of 960 mg to 240 mg, the medical oncology prior authorization process will continue.
  • the request is not changed from the daily dose of 960 mg to 240 mg, the medical oncology prior authorization process will continue and will not be denied for medical necessity.

Sources

1. Phase 1 trial data: Hong et al. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors | New England Journal of Medicine
2. Phase 2 trial data: Skoulidis et al. Sotorasib for Lung Cancers with KRAS p.G12C Mutation
3. Phase 3 trial data: Sotorasib (960 mg or 240 mg) once daily in patients with previously treated KRAS G12C-mutated advanced NSCLC – PubMed
4. National Comprehensive Cancer Network^® (NCCN) Guidelines
5. Sotorasib in KRAS p.G12C–Mutated Advanced Pancreatic Cancer | New England Journal of Medicine