Dr Dotan on Gemcitabine and Nab-Paclitaxel in Treatment-Naive, Older Pancreatic Cancer

“[These findings indicate that] we can attenuate doses; we can give less treatment and achieve the same outcome as we would with standard dosing.”

Efrat Dotan, MD, an innovation faculty member at the Penn Center for Cancer Care Innovation and the executive medical director of the Ann B. Barshinger Cancer Institute at Penn Medicine Lancaster General Health, discusses the phase 2 ECOG-ACRIN EA2186 (GIANT) trial (NCT04233866) evaluating gemcitabine and nab-paclitaxel (Abraxane) vs 5-fluorouracil (5-FU), leucovorin, and liposomal irinotecan in older patients with treatment-naive, metastatic pancreatic cancer.

GIANT was an important trial because this older population of patients with metastatic pancreatic cancer had not been specifically studied before, Dotan began. The study enrolled patients who were at least 70 years of age with geriatric vulnerabilities, she continued. Patients were randomly assigned to receive modified gemcitabine and nab-paclitaxel or dose-reduced 5-FU plus leucovorin and liposomal irinotecan, she added.

Findings from the study showed that there were minimal differences in efficacy outcomes between the 2 arms, Dotan explained. The median overall survival values in the intention-to-treat population were comparable between the investigational (n = 76) and control (n = 78) arms, at 4.7 months (95% CI, 4.1-7.4) and 4.4 months (95% CI, 3.1-8.9), respectively (HR, 1.12; 95% CI, 0.76-1.66; P = .72).

In terms of safety, the toxicity rates were largely similar, with differences in the types of toxicities, Dotan said. For example, there were higher rates of neuropathy in the gemcitabine and nab-paclitaxel arm, whereas a greater incidence of diarrhea was observed in the 5-FU leucovorin and liposomal irinotecan arm, she said. Overall, the rates of grade 3 toxicities were approximately the same, she added.

Of note, patients who were able to remain on treatment for at least 4 weeks across arms (n = 127) achieved a median OS of 8.0 months (95% CI, 5.9-10.0), Dotan emphasized. This suggests that doses can be attenuated, leading to patients receiving less treatment while still achieving the same outcomes as standard dosing, she explained. How to best identify patients who would be candidates for this approach remains an open question, she said.

Patients with better baseline nutrition and quality of life measures were among those who achieved better outcomes, Dotan said. These findings underscore the importance of treatment personalization, she concluded.