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Sotorasib as Fourth-Line Treatment in Pancreatic Cancer: A Case Report and Literature Review
Ifeanyi David Onukogu1, Georgio Medawar2, Yashvin Onkarappa Mangala1
1Division of Hematology/Oncology, Roger Williams Medical Center/Boston University, Providence, RI.
Abstract:
The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell proliferation and is present in 90% of unresectable or metastatic pancreatic adenocarcinomas. Of these, the G12C variant of K-RAS genes accounts for 1-2% of mutations. A 65-year-old woman initially diagnosed with T3N0M0 pancreatic adenocarcinoma, underwent six cycles of neoadjuvant chemotherapy with mFOLFIRINOX followed by Whipple procedure. Her pathological stage was T4N2. She then received adjuvant mFOLFIRINOX but unfortunately her disease progressed through multiple lines of chemotherapy. Molecular analysis by Next Generation Sequence(NGS) panel revealed KRAS G12C mutation. Based on this mutational status, she was started on Sotorasib to which she had clinical response lasting for about 11 months prior to disease progression. Off-label use of Sotorasib as fourth-line treatment in our patient with KRAS G12C mutated pancreatic cancer was efficacious and relatively well tolerated.
Insights
KRAS G12C mutations drive pancreatic cancer. Targeting this mutation with Sotorasib showed efficacy in a patient with advanced pancreatic adenocarcinoma, offering a potential new treatment avenue.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Exocrine pancreatic cancer pathogenesis involves key mutations like KRAS, TP53, CDKN2A, and SMAD4.
- The KRAS oncogene is crucial for tumor cell proliferation, found in 90% of advanced pancreatic adenocarcinomas.
- The KRAS G12C variant represents a small but targetable subset of these mutations.
Observation:
- A patient with advanced pancreatic adenocarcinoma (T4N2) progressed despite multiple chemotherapy lines, including mFOLFIRINOX.
- Next-Generation Sequencing identified a KRAS G12C mutation in the patient's tumor.
- The patient received off-label Sotorasib, a targeted therapy for KRAS G12C.
Findings:
- Sotorasib treatment resulted in a clinical response lasting approximately 11 months.
- The targeted therapy demonstrated efficacy in a patient with refractory pancreatic cancer.
- Sotorasib was relatively well-tolerated as a fourth-line treatment.
Implications:
- Targeting KRAS G12C mutations with Sotorasib is a viable therapeutic strategy for advanced pancreatic cancer.
- Personalized medicine approaches based on molecular profiling can improve treatment outcomes.
- Further research into KRAS G12C-targeted therapies is warranted for pancreatic cancer management.
