Is there a survival benefit of adding immunotherapy to chemotherapy in patients with advanced gallbladder cancer?

Survival Benefit of Immunotherapy in Advanced Gallbladder Cancer

Yes, adding immunotherapy to chemotherapy provides a significant survival benefit in advanced gallbladder cancer, and this combination is now the standard of care for first-line treatment. 1

First-Line Treatment: The New Standard

The combination of gemcitabine plus cisplatin plus immunotherapy (durvalumab or pembrolizumab) is the recommended standard of care for patients with advanced, unresectable, or metastatic gallbladder cancer. 1

Specific Survival Data

• Durvalumab-based regimen: The standard regimen consists of gemcitabine 1000 mg/m² plus cisplatin 25 mg/m² on days 1 and 8 of each 21-day cycle, combined with durvalumab 1500 mg on day 1 of each cycle, achieving a median overall survival of 12.9 months versus 11.3 months with chemotherapy alone (HR 0.76,95% CI 0.64-0.91). 1

• This represents approximately a 1.6-month survival improvement with the addition of immunotherapy, which is statistically significant and clinically meaningful in this aggressive malignancy. 1

Treatment Protocol

Continue combination therapy for up to 8 cycles, followed by durvalumab maintenance until disease progression or unacceptable toxicity. 1

• For patients weighing ≥30 kg: Durvalumab 1500 mg every 3 weeks in combination with chemotherapy, then 1500 mg every 4 weeks as a single agent. 2

• For patients weighing <30 kg: Durvalumab 20 mg/kg every 3 weeks in combination with chemotherapy, then 20 mg/kg every 4 weeks as a single agent. 2

Supporting Evidence from Real-World Experience

Beyond the pivotal trial data, clinical case reports demonstrate dramatic responses:

• Complete pathological response: A case of locally-advanced gallbladder adenocarcinoma with peritoneal metastasis achieved near-complete pathological response (ypT1aN0) after 8 cycles of cisplatin-gemcitabine-durvalumab, enabling successful conversion to R0 resection. 3

• Objective response rates: In a retrospective analysis of PD-1 inhibitor-based treatment, the objective response rate was 30.2% and disease control rate was 79.2% at 3 months, with median PFS of 7 months and median OS of 12 months. 4

• Combination therapy superiority: Immunotherapy combined with chemotherapy showed significantly better outcomes than immunotherapy alone (mPFS 9 vs. 3 months, mOS 13 vs. 8 months, p<0.001). 4

Critical Clinical Pitfall to Avoid

Do not use gemcitabine-cisplatin alone as first-line therapy for advanced gallbladder cancer—this is now suboptimal care given the proven survival benefit of adding immunotherapy. 1

• The historical standard of gemcitabine-cisplatin alone (from the ABC-02 trial era) achieved median OS of only 11.7 months versus 8.1 months with gemcitabine alone. 1

• Adding immunotherapy improves upon this baseline, making chemotherapy-only regimens outdated. 1

Safety Profile

The addition of immunotherapy to chemotherapy demonstrates acceptable toxicity:

• Most treatment-related adverse events are grade 1-2, with immune-related adverse events occurring in approximately 32.8% of patients. 5

• The highest grade 3-4 adverse effects remain chemotherapy-related: thrombocytopenia (7.75%) and neutropenia (3.1%). 5

Alternative Immunotherapy Option

Pembrolizumab can be substituted for durvalumab based on the Keynote-966 trial, though the benefit was primarily driven by intrahepatic cholangiocarcinoma rather than extrahepatic disease. 1

Context: Historical Perspective

Prior to the immunotherapy era, the prognosis for advanced gallbladder cancer was dismal:

• Median survival without chemotherapy was only 2.5-6 months. 1

• Even with aggressive surgical management, 5-year survival rates remain modest at 5-10% for gallbladder cancer. 6

• The addition of immunotherapy represents the first major therapeutic advance in over a decade for this disease. 3