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Advanced Gastric Cancer

CE / CME

Cases and Challenges in the Optimal Treatment of Advanced Gastric Cancer

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurse Practitioners: 1.00 Nursing contact hours, includes 1.00 hour of pharmacotherapy credit

Released: April 27, 2023

Expiration: April 26, 2024

Steven Maron
Steven Maron, MD
CME/CE Information

Activity

Progress
1
Course Completed

Managing Side Effects of Treatment With T-DXd

Overall, the side effects of T-DXd are manageable, and include hematologic and GI toxicities, which were reported in 30% or more of patients. Frequent all-grade side effects of T-DXd include nausea, diarrhea, vomiting, and constipation, each of which is fairly common. However, the rate of grade ≥3 toxicities is low, and includes 4.8% nausea and 2.4% diarrhea.28 In DESTINY-Gastric01, grade ≥3 adverse effects were reported in 85.6% of patients receiving T-DXd and 56.5% of patients receiving chemotherapy.26,27 In that trial, grade ≥3 neutropenia (51%), anemia (38%), and decreased white blood cells (21%) were reported with T-DXd. 

In clinical use, T-DXd is administered intravenously at a dosage of 6.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity. Dose reductions to 5.4 mg/kg and 4.4 mg/kg may be used to manage toxicity.28

A special concern for patients treated with T-DXd is development of ILD/pneumonitis, which can progress rapidly and may be fatal if unmanaged. In DESTINY-Gastric01, 12.4% of patients developed ILD, of which 2.4% were grade 3 or higher in severity.26,27 NPs and PAs managing patients treated with T-DXd must be on alert for ILD signs and symptoms in order to ensure quick diagnosis and intervention.

 

Expert Insights From Dr Maron: Safety profile of T-DXd

 

 

Management of T-DXd–Associated ILD
In pooled data from 9 studies of patients treated with T-DXd, several risk factors stand out. Highest risk for ILD was associated with longer time from diagnosis (≥4 vs <4 years), moderate/severe renal impairment, and higher dosage of the drug (>6.4 mg/kg every 3 weeks).33 Lung comorbidities and SpO2 lower than 95% also increase risk.33 In this analysis, the overall rate of ILD across all studies was 15.4%, of which the majority of cases were grade 1 or 2; rates were highest in studies with breast and lung cancer, and lower in gastric and colorectal cancer.33 Figure 3 illustrates suggested monitoring and management of ILD in patients treated with T-DXd.28,33

 

Figure 3. Management of ILD Associated With T-DXd28,33

 

Expert Insights From Dr Maron:Approach to monitoring and managing ILD

 

NCCN Guidelines: Second-Line Approach to Advanced or Metastatic GC
In current guidelines, the following approach is recommended for patients who have progressed after initial therapy for metastatic disease4: 

  • HER2-positive adenocarcinoma: T-DXd (preferred)
  • HER2-negative disease: ramucirumab plus paclitaxel (preferred)
  • Other options: single-agent docetaxel, irinotecan ± 5-flurouracil
  • Third line and beyond: trifluridine/tipiracil  

As more newly diagnosed patients receive first-line ICI therapy, the question of whether an ICI can be used in subsequent lines for patients with dMMR/MSI-H or high TMB tumors remains an area of inquiry. At present, nivolumab and pembrolizumab are recommended for such patients only if they were not previously treated with an ICI.4,8 A third ICI, dostarlimab, also has demonstrated efficacy in dMMR/MSI-H solid tumors in the GARNET trial and is indicated only for such patients.34 The tumor-agnostic NTRK inhibitors entrectinib and larotrectinib may be considered for patients whose tumors are positive for NTRK fusion mutation who have progressed after other options.4,35,36 Selpercatinib may be considered for patients whose tumors contain a RET gene fusion and have progressed on other treatment.4,37

 

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