As survival times for metastatic gastric cancer patients extend, managing long-term toxicity is paramount. Clinicians typically administer only 6-8 cycles of oxaliplatin to prevent severe, cumulative peripheral neuropathy, allowing for longer, better-tolerated maintenance therapy with biologics.
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The Right Choice trial shows CDK4/6 inhibitors are safer and better at delaying cancer progression than chemotherapy for patients with visceral metastases. However, this advantage doesn't translate to longer overall survival, suggesting the key benefit is improved quality of life and a less complex treatment regimen rather than longevity.
For patients over 75 with metastatic gastric cancer, a common practice is to reduce the oxaliplatin dose from 85 to 65 mg/m² and universally omit the 5-FU bolus from the FOLFOX regimen. This pragmatic approach aims to maintain efficacy while minimizing toxicity in a more vulnerable population.
Counterintuitively, adding palbociclib to maintenance therapy showed a favorable quality of life in the PATINA trial. Despite known toxicities, the drug delayed the time to first symptom progression. This suggests that the benefit of superior disease control can outweigh the negative impact of treatment side effects on patient-reported outcomes.
When treating elderly patients (e.g., age 80+) with metastatic breast cancer, clinicians may prioritize quality of life over marginal overall survival gains seen in clinical trials. This justifies using a better-tolerated CDK4/6 inhibitor like palbociclib, even though ribociclib has demonstrated a statistical survival benefit, especially when patients have comorbidities or a preference for fewer side effects.
The HORIZON-GEA-01 trial for zanidatumab in gastric cancer mandated prophylactic loperamide (4mg BID) for all patients. This was necessary to manage the high rates of diarrhea (up to 80% of patients), a significant GI toxicity associated with the drug's mechanism of action.
The development of PARP-1 selective inhibitors like seriparib signals a shift in drug innovation. Instead of only chasing higher efficacy, these new agents aim for a more favorable toxicity profile (less GI toxicity, fewer dose discontinuations) to improve patient quality of life and treatment adherence.
Comparing control arms from the TOGA (11 months OS), KEYNOTE-811 (16 months), and HORIZON (19 months) trials reveals a steady improvement in patient outcomes. This trend, likely due to better second-line therapies and supportive care, makes it harder for new agents to show a relative benefit.
Clinicians advise against continuing targeted agents like zolbituximab or trastuzumab after disease progression in gastroesophageal cancer. The biological heterogeneity of this cancer type means that if a targeted therapy isn't working, it's unlikely to provide benefit with a different chemotherapy backbone.
Unlike neuropathy from vincristine which peaks during therapy, polatuzumab vedotin exhibits a "late cresting phenomenon." Patients can experience worsening neuropathy even after completing their sixth and final cycle, a crucial detail for patient counseling and proactive management.
Clinical trial data shows that despite specific toxicities, antibody-drug conjugates (ADCs) can be better tolerated overall than standard chemotherapy. For example, trials for both sacituzumab govitecan and dato-DXd reported fewer patients discontinuing treatment in the ADC arm compared to the chemotherapy arm.
