Sotorasib-panitumumab shows efficacy against KRAS G12C-mutated mCRC

In the recent CodeBreaK 101 study, sotorasib, in combination with panitumumab, has been demonstrated to be safe and effective among patients with chemorefractory Kirsten rat sarcoma virus (KRAS) G12C-mutated metastatic colorectal cancer (mCRC).1 The positive results showed promise of this novel combination therapy as a new standard of care (SoC) for the treatment of KRAS G12C-mutated mCRC.1

Colorectal cancer (CRC) is the second and third most common cancer in women and men, respectively.2 It accounts for around 10% of all cancer-related deaths worldwide.2 About 3% of CRC tumors are found to carry the oncogenic KRAS G12C mutation.1 Unfortunately, the majority of patients in this group either show no response to therapy or develop drug resistance to monotherapy of KRAS G12C inhibitors such as sotorasib.3 Panitumumab is an epidermal growth factor receptor (EGFR) inhibitor for treating mCRC.4 It is suggested that therapies combining sotorasib and panitumumab could result in a more complete inhibition of tumor cell growth and improve treatment efficacy among patients with chemorefractory KRAS G12C-mutated mCRC.1,5

The CodeBreaK 101 study was a phase 1b, multicenter study which evaluated the safety and efficacy of the sotorasib-panitumumab regimen among patients with chemorefractory KRAS G12C-mutated mCRC.1 Eligible patients were those who had not received KRAS G12C inhibitors and had progressed on ≥1 prior treatment for advanced disease.1 A total of 40 patients were enrolled to receive oral sotorasib 960mg daily together with panitumumab 6mg/kg intravenously once every 2 weeks.1 The study’s key efficacy endpoints included anti-tumor efficacy, tumor response, progression-free survival (PFS), and overall survival (OS).1

In this trial (data cutoff date: June 24, 2022), sotorasib-panitumumab achieved a disease control rate (DCR) of 93% (95% CI: 79.6-98.4) and a confirmed objective response rate (ORR) of 30% (95% CI: 16.6-46.5), which did not differ between the tumor locations.1 A reduction of the Response Evaluation Criteria in Solid Tumors (RECIST) target lesions was also observed in 88% of patients.1 The median duration of response was 4.4 months, while the median duration of treatment was 5.9 months.1

With a median follow-up of 11 months, sotorasib-panitumumab achieved a median PFS of 5.7 months, along with a 9-month PFS rate of 12.3%.1 Regarding OS, the median OS was not reached (95% CI: 10.4-Not evaluable) after a median follow-up of 8.8 months.1 The 9-month OS rate was reported to be 82.5%.1

The majority of patients treated with sotorasib-panitumumab experienced treatment-related adverse events (TRAEs).1 About 23% had grade 3 TRAEs, whereas no ≥grade 4 TRAEs or TRAEs leading to drug discontinuation were reported.1 The most common TRAEs of any grade included dermatitis acneiform, rash, diarrhea, dry skin, pruritus, and nausea.1 These findings were consistent with the known safety profiles of sotorasib and panitumumab.1

Overall, sotorasib-panitumumab was well tolerated and efficacious among patients with chemorefractory KRAS G12C-mutated mCRC.1 The favorable results supported the possible future use of sotorasib-panitumumab as a new SoC for the treatment of KRAS G12C-mutated mCRC.1

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