Solid Tumors: Pharmacy Updates with Dr Monica Quinn
Conference:
2024 West Oncology Virtual Conference for Advanced Patient Practicioners (APP)
Presenter:
Monica Quinn, PharmD, MBA, Director of Pharmacy Operations, West Cancer Center
At the 2024 West Oncology Virtual Conference for Advanced Patient Practicioners (APP), Dr Monica Quinn, Director of Pharmacy Operations at West Cancer Center, presented an overview of recent drug approvals and therapy updates in the treatment of solid tumors, with a focus on pharmacological developments and FDA approvals from 2023 to 2024. Her presentation reviewed several novel therapies and their clinical applications, supporting pivotal trial data, and practical considerations for their use in oncology practice.
Monoclonal Antibodies
Monoclonal antibodies, including anti-programmed death 1 (PD1) agents have continued to play a transformative role in cancer treatment. Dr. Quinn highlighted two new approvals in this class:
Toripalimab: This anti-PD1 monoclonal antibody was approved for use in metastatic or recurrent nasopharyngeal carcinoma (NPC). The pivotal JUPITOR-02 Phase III trial demonstrated improved progression-free survival (PFS) when combined with chemotherapy versus chemotherapy alone. While effective, she noted toripalimab is associated with notable adverse events, including fatigue, hypothyroidism, and nausea. Its dosing varies depending on its use as a monotherapy or in combination, with stringent requirements to mitigate immune-related adverse effects.
Tislelizumab: Also an anti-PD1 agent, tislelizumab received approval for unresectable or metastatic esophageal squamous cell carcinoma (ESCC) in patients who have had prior systemic chemotherapy. The RATIONALE-302 trial confirmed an overall survival (OS) benefit for tislelizumab over chemotherapy (8.6 months vs. 6.3 months). The safety profile includes increased AST, anemia, and hypothyroidism, highlighting the need for close monitoring of patients on this agent.
Kinase Inhibitors
Dr Quinn noted this class of drugs has seen significant advancements in 2024, with several agents offering targeted approaches to various malignancies:
Fruquintinib: This is a vascular endothelial growth factor (VEGF) receptor kinase inhibitor (TKI) approved for metastatic colorectal cancer (mCRC) in previously treated patients. The FRESCO-02 trial showed a median OS improvement to 7.4 months versus 4.8 months with placebo. Key side effects of this agent include hypertension and hand-foot syndrome, necessitating careful pre-treatment evaluation and ongoing monitoring.
Repotrectinib: This multikinase TKI targets tumors with ROS1 and NTRK gene fusions, providing an option for patients with ROS1-positive non-small cell lung cancer (NSCLC). In the TRIDENT-1 study, repotrectinib demonstrated a 79% overall response rate (ORR) in TKI-naïve patients. Common side effects such as dizziness and peripheral neuropathy should be monitored in patients on this agent as they may impact patient quality of life.
Capivasertib: Approved for hormone receptor-positive, HER2-negative breast cancer with specific genetic alterations, capivasertib works by inhibiting the AKT tyrosine kinase. The CAPItello-291 trial revealed a median PFS benefit (7.3 vs. 3.1 months) for patients on this agent versus placebo. Side effects include hyperglycemia, diarrhea, and anemia, highlighting the need for metabolic monitoring.
Gamma Secretase Inhibitor
Nirogacestat: This first-in-class gamma secretase inhibitor offers a novel option for patients with desmoid tumors requiring systemic therapy. The DeFi trial demonstrated substantial efficacy, with a median PFS not reached in the treatment arm compared to 15.1 months with placebo. Ovarian toxicity and other side effects, however, warrant careful consideration when used in female patients of reproductive age.
Interleukin-15 Receptor Agonist
Nogapendekin alfa inbackicept (NAI): This agent was approved for use in patients with non-muscle invasive bladder cancer (NMIBC) that is non-responsive to BCG therapy. Findings from the QUILT – 3.032 Trial showed a complete response rate of 62%, with 58% of patients having a response duration of >12 months. Principle adverse events associated with this agent included increased creatinine, dysuria, hematuria, and urinary frequency. Treatment should be discontinued if disease persists after second induction or if progression or unacceptable toxicity occurs.
Bispecific Monoclonal Antibody
Tarlatamab: A DLL3-targeting bispecific T-cell engager, tarlatamab has been approved for extensive-stage small cell lung cancer (ES-SCLC) following platinum-based chemotherapy based on findings from the DeLLphi-301 trial, which showed a 40% response rate in treated patients. While efficacy is promising, its use is complicated by a high incidence of cytokine release syndrome (CRS) and neurotoxicity, requiring pre-treatment with dexamethasone and close observation post-infusion.
Novel FDA Indications and Withdrawals
Dr. Quinn concluded by reviewing recent changes in FDA regulatory activity. Highlights included new indications for drugs like durvalumab in non-small cell lung cancer and ribociclib in breast cancer. She also noted two withdrawals: mobocertinib (for NSCLC) and infigratinib (for cholangiocarcinoma), emphasizing the evolving nature of oncology drug approvals.
Clinical Implications and Future Directions
Dr. Quinn emphasized the importance of these advancements in expanding the therapeutic arsenal against solid tumors. However, she cautioned that the adverse event profiles of these drugs necessitate careful patient selection and vigilant monitoring. She also highlighted the need for further research to validate their long-term efficacy and integrate them seamlessly into clinical practice. Dr. Quinn also expressed optimism about the oncology pipeline, noting that these updates represent significant steps forward in personalized and precision medicine for many patients.
Speaker Disclosure Information: Dr Quinn reported no relevant disclosures for this presentation.
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You can see the full presentation by Dr Quinn from the 2024 West Oncology Virtual Conference for Advanced Patient Practicioners (APP) here.