Sotorasib
Regulatory sources consulted
- openfda-label-8f611e67-8c58-4413-8b81-a200fa7f30e8
- ema-epar-EMEA/H/C/005522
- aemps-cima-1211603004
- PubMed PMID:37870968 ↗
- PubMed PMID:38637634 ↗
- PubMed PMID:39732595 ↗
- PubMed PMID:34776511 ↗
- PubMed PMID:38686056 ↗
- OpenFDA · L01XX73
- RxNorm rxcui 2550714 ↗
Approved indications
- Treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.
- In combination with panitumumab, for the treatment of adult patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC) as determined by an FDA approved-test, who have received prior fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy.
Contraindications
Absolute
- None.
Clinical warnings
- Major warning · Hepatotoxicity: Transaminase elevations have been observed. Monitor liver function tests prior to start and during treatment. — FDA
- Major warning · Interstitial Lung Disease (ILD)/Pneumonitis: ILD/pneumonitis, including fatal cases, has been reported. Monitor patients for new or worsening pulmonary symptoms and withhold treatment if suspected. — FDA
Drug interactions
- HighProton Pump Inhibitors (PPIs)A02BC
Mechanism: The solubility of sotorasib is pH-dependent. Coadministration with gastric acid-reducing agents decreases sotorasib concentrations, which may reduce its efficacy.
Recommendation: Avoid coadministration with PPIs and H2 antagonists. If an acid-reducing agent cannot be avoided, administer sotorasib 4 hours before or 10 hours after a local antacid.
FDA label
- HighStrong CYP3A4 Inducers
Mechanism: Sotorasib is a CYP3A4 substrate. Coadministration with a strong CYP3A4 inducer decreases sotorasib concentrations, which may reduce its efficacy.
Recommendation: Avoid coadministration.
FDA label
- HighSensitive CYP3A4 Substrates
Mechanism: Sotorasib is a CYP3A4 inducer. Coadministration decreases substrate concentrations, which may reduce the efficacy of the substrate.
Recommendation: Avoid coadministration with CYP3A4 substrates for which minimal concentration changes may lead to therapeutic failures. If coadministration cannot be avoided, adjust the substrate dosage.
FDA label
- HighP-gp Substrates with narrow therapeutic index
Mechanism: Sotorasib is a P-gp inhibitor. Coadministration increases substrate concentrations, which may lead to serious toxicities.
Recommendation: Avoid coadministration. If coadministration cannot be avoided, decrease the substrate dosage in accordance to its Prescribing Information.
FDA label
Adverse events
Common (≥1%)
diarrhea · musculoskeletal pain · nausea · fatigue · hepatotoxicity · cough · rash · dry skin · stomatitis
Rare but serious
severe hepatotoxicity · interstitial lung disease · pneumonitis
Pregnancy and lactation
There are no available data on LUMAKRAS use in pregnant women. Advise not to breastfeed during treatment and for 1 week after the last dose.
Recent literature (PubMed)
Ensayo de fase 3 que demuestra que sotorasib (960 mg) más panitumumab mejoró significativamente la supervivencia libre de progresión en comparación con el tratamiento estándar en pacientes con cáncer colorrectal metastásico quimiorrefractario con mutación KRAS G12C (5.6 meses vs 2.2 meses; HR 0.49).
Revisión exhaustiva sobre la patobiología de RAS, los enfoques terapéuticos para diversas neoplasias, y las estrategias de combinación. Destaca el éxito de sotorasib y adagrasib como los primeros inhibidores de KRAS G12C aprobados, abriendo una nueva era en el tratamiento del cáncer.
Revisión que aborda los nuevos desafíos tras la aprobación de sotorasib y adagrasib. Se enfoca en los mecanismos de resistencia a los inhibidores de KRAS y las estrategias de tratamiento combinado que se están desarrollando para mejorar la respuesta de los pacientes.
Revisión que resume el paso de KRAS de ser un objetivo 'no farmacológico' a uno tratable, destacando los avances con inhibidores de KRAS G12C como sotorasib (AMG510). Discute los mecanismos de resistencia y posibles terapias de combinación.
Artículo de revisión sobre el tratamiento del cáncer de páncreas. Señala que sotorasib tiene eficacia clínica en cáncer de pulmón, pero su uso en cáncer de páncreas es limitado ya que la mutación KRAS G12C solo se detecta en el 2-3% de los casos de PDAC.