Chemotherapy Also Benefits Older Patients with Pancreatic Cancer

Pancreatic cancer is usually diagnosed after age 65, with a median age at diagnosis of 70. Most patients have advanced disease at diagnosis, meaning the cancer has spread beyond the pancreas. Treatment options are limited at this stage, and surgery is usually not possible. This adversely affects treatment and survival rates.

Current Standard Treatment

Treatment for pancreatic cancer varies with the stage of disease and the patient's general health. Surgery is the most effective treatment at an early stage. When cancer is diagnosed at an advanced stage, however, surgery is usually not possible and chemotherapy becomes the mainstay of treatment. A small number of patients may benefit from targeted treatments or immunotherapy based on genomic and genetic testing results. The most common chemotherapy regimens include FOLFIRINOX (a combination of 5-FU, leucovorin, irinotecan and oxaliplatin) and gemcitabine combined with nab-paclitaxel.

The GIANT Study Presented at ASCO 2024

ASCO 2024 featured findings from the phase-2 randomized GIANT study, providing important information about older patients with previously untreated metastatic pancreatic cancer.

• Patient Selection:

  • The study included patients aged 70 years or older.
  • A geriatric assessment classified patients as "fit" (no geriatric abnormalities), "vulnerable" (mild-to-moderate abnormalities) or "frail" (severe abnormalities).

• Treatment Groups:

  • "Fit" Patients: Received standard treatment outside the study.
  • "Frail" Patients: Received supportive care outside the study.
  • "Vulnerable" Patients:
    • A total of 176 patients were randomized to two treatment groups:
      • Reduced-dose 5-fluorouracil (5-FU), leucovorin and liposomal irinotecan (88 patients).
      • Modified gemcitabine and nab-paclitaxel (88 patients).
    • The 5-FU combination was started by 79 patients, while 75 started gemcitabine and nab-paclitaxel.

• Assessment and Monitoring:

  • Patients were assessed every 8 weeks until disease progression or intolerance.
  • Median patient age in the study was 77 years.
  • Of the participants, 61.9% were aged 75 years or older.
  • Approximately half were women, and 81.5% were White.
  • Most (87.5%) had a performance status of 0 or 1.

Findings:

• Overall Survival: Median overall survival was 4.7 months in the gemcitabine and nab-paclitaxel arm and 4.4 months in the 5-FU combination group.
• Treatment Continuation: Median survival increased to 8.0 months in patients who received at least two treatment cycles.
• Performance Status: Survival was markedly worse in patients with a performance status of 2 than in those with a performance status of 0 (1.4 months versus 6.9 months).
• Adverse Events: More than half of patients experienced grade 3 or higher adverse events. Adverse-event profiles differed between regimens: peripheral neuropathy was more frequent with gemcitabine plus nab-paclitaxel, while diarrhea was more frequent with the 5-FU combination.

Key Takeaways

The study showed limited treatment tolerance in older, vulnerable patients, many of whom could not start or complete treatment. Both chemotherapy regimens nevertheless offer suitable options for patients able to tolerate treatment. The importance of geriatric assessment, rather than relying on performance status alone, was also emphasized. Such assessment may better identify patients who can tolerate treatment and support the development of suitable treatment strategies.