First-line treatment with FOLFOXIRI for advanced pancreatic cancer in clinical practice: Patients' outcome and analysis of prognostic factors

315 Background: The combination of capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer patients has proved beneficial in terms of median survival duration, objective radiological response rate and decrease in tumour marker levels from baseline. In the phase I study of capecitabine and lapatinib carried out in advanced solid tumors, the optimal tolerated regimen was determined to be lapatinib 1,250 mg plus capecitabine 2,000 mg/m2/day. At these dose levels, the combination was well tolerated with few grade 3 toxicities and no grade 4 toxicity. Our preclinical work suggested synergistic activity of capecitabine and lapatinib in pancreatic cancer. We initiated a study of this combination in the first-line therapy of metastatic pancreas cancer. Methods: This was a single-arm multicenter study in patients with chemotherapy-naive metastatic pancreatic cancer. The primary endpoint was overall survival. The study was designed as a Simons two-stage optimal design and was divided into two stages. The first stage was to recruit up to 12 patients. If at least seven of these patients survived for at least six months, then a further 20 patients would be enrolled into the study. If six or fewer of the initial 12 patients met the specified study survival criteria, the study would be halted. Treatment was to be administered until disease progression or until withdrawal from the study due to unacceptable toxicity or other reasons. Clinical and laboratory parameters were assessed to evaluate disease response and toxicity of therapy. The study patients received lapatinib 1,250 mg/day, plus capecitabine 2000 mg/m2/day on days 1-14 every 21 days. Results: Nine patients were enrolled. Seven of these patients did not achieve the interim protocol response requirement of survival for at least 6 months, to allow for the study to continue to the second cohort of patients. Median overall survival from first dose was 4 months. Median time on treatment was 2 months. There were no objective responses. There were no unexpected toxicities. Conclusions: The addition of lapatinib to capecitabine does not improve overall survival in the first-line treatment of advanced pancreatic cancer patients. [Table: see text]

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PD-1 antibody combined with paclitaxel (albumin bound) and gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps4665 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS4665-TPS4665

Author(s):

Jiujie Cui ◽

Jiayu Yao ◽

Yu Wang ◽

Yiyi Liang ◽

Yongchao Wang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Checkpoint Inhibitors ◽

Tumor Therapy ◽

Advanced Pancreatic Cancer ◽

Metastatic Pancreatic Cancer ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

First Line Treatment

TPS4665 Background: Pancreatic cancer is a malignant tumor with limited therapeutic strategies and poor prognosis. About 60% of the patients have metastasis disease at time of diagnosis and lose the opportunity for surgery. Thus, therapy based on drugs becomes a vital part in pancreatic cancer. In 2013, MPACT showed that albumin-bound paclitaxel combined with gemcitabine in the treatment of metastatic pancreatic cancer could increase the mOS from 6.6 months to 8.7 months (HR = 0.72, 95% CI: 0.62-0.83; P < 0.001). Nowadays, the immunosuppressive checkpoint inhibitors acting on PD-1/PD-L1 pathway have shown a significant efficacy in enhancing tumor immune surveillance and anti-tumor immune response. In 2018, two studies reported in ASCO showed the preliminary efficacy of albumin paclitaxel, gemcitabine and PD-1 inhibitor in the treatment of advanced pancreatic cancer. Among patients who have not received treatment before, the disease control rate was even up to 100%. Therefore, this study will further explore the domestic PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as the first-line treatment of advanced pancreatic cancer among Chinese pancreatic cancer patients. Methods: This is a prospective, single-armed, exploratory, investigator initiated trial to explore the efficacy and safety of PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as first-line treatment of metastatic pancreatic cancer. This study is, to our knowledge, the first one to test the efficacy and safety of PD-1 antibody on metastatic pancreatic cancer patients among Chinese population. Survival index is median survival estimated by Kaplan-Meier and draw the survival curve. The response rate was compared by χ 2 test / Fisher test. All primary and secondary outcomes will be analyzed on the full analysis set. PD-1 antibody, 200mg, D1 administration; paclitaxel (albumin binding type), 125mg/m2, D1, 8 days administration; gemcitabine, 1000mg/m2, D1, 8 days administration, every 21 days as a cycle and PD-1 antibody (200mg, D1, every 21 days) single drug maintenance treatment is given after the completion of 6 cycle chemotherapy. Major eligibility criteria is that each participant must have metastatic pancreatic cancer confirmed by histology or cytology and has never received systemic anti-tumor therapy before. So far, 11 of planned 20 patients have been enrolled. Clinical trial information: NCT04181645 .

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