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Association details:
| Biomarker: | PTEN deletion + KRAS G12C |
|---|---|
| Cancer: | Bladder Cancer |
| Drug: | Lumakras (sotorasib) (KRAS G12C inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
KRAS G12C mutated NSCLC and bladder cancer xenografts treated with sotorasib and adagrasib in combination with mTOR inhibitors show improved antitumor activity of nab-sirolimus vs everolimus
Published date:
10/12/2022
Excerpt:
Athymic mice bearing subcutaneous KRAS G12C and STK11-mutated NSCLC xenografts NCI-H2030 and NCI-H2122 and KRAS G12C-mutated and PTEN-null UMUC3 bladder cancer were treated with saline, mTOR inhibitors nab-sirolimus or everolimus (in NCI-H2030 and H2122) at clinically relevant and equal weekly dose of 15 mg/kg/wk, KRAS inhibitors sotorasib or adagrasib (in NCI-H2122)...In NCI-H2030 xenografts (n = 6 tumors/group), both nab-sirolimus and everolimus as single agent demonstrated tumor growth inhibition (TGI: nab-sirolimus 68% vs everolimus 22%, P = ns). When combined with KRAS inhibitor sotorasib, there was greater activity with nab-sirolimus than with everolimus (TGI: nab-sirolimus + sotorasib 109% vs everolimus + sotorasib 53%, P = 0.0008). Combining nab-sirolimus with sotorasib showed significantly greater TGI (109%) compared with single agent nab-sirolimus (68%, P = 0.0102) or sotorasib (20%, P = 0.0002). Similar results were seen with NCI-H2122 and UMUC3 cell lines.
Secondary therapy:
nanoparticle albumin-bound rapamycin
