The addition of cisplatin to gemcitabine and nab-paclitaxel resulted in encouraging activity in patients with previously untreated advanced pancreatic cancer, despite not having demonstrated the prespecified number of complete responses to meet the primary endpoint of a phase Ib/II clinical trial (NCT01893801), according to findings published in JAMA Oncology.
Daniel D. Von Hoff, MD, FACP
The addition of cisplatin to gemcitabine and nab-paclitaxel (Abraxane) resulted in encouraging activity in patients with previously untreated advanced pancreatic cancer, despite not having demonstrated the prespecified number of complete responses (CRs) to meet the primary endpoint of a phase Ib/II clinical trial (NCT01893801), according to findings published in JAMA Oncology.1,2
In 24 evaluable patients, the triplet demonstrated a CR rate, as assessed by RECIST v1.1 criteria, of 8% (n = 2), which fell below the primary endpoint of 25%. Additionally, the partial response rate was 62% (n = 15) and the stable disease rate was 17% (n = 4), which led to an objective response rate of 71% and a disease control rate of 88%.
“By adding the drug cisplatin to the current standard of care, nab-paclitaxel plus gemcitabine, we demonstrated substantial clinical activity. The results of this triple-drug regimen are very encouraging for these patients,” study author Daniel D. Von Hoff, MD, FACP, physician-in-chief at Translational Genomics Research Institute, stated in a press release.
Approximately 80% of patients with pancreatic cancer will present with advanced disease and a poor prognosis due to limited treatment options. Investigators hypothesized that exploiting the DNA-repair deficiencies of the disease with a DNA-damaging agent like cisplatin could result in improved outcomes.
In the single-arm, open-label, phase Ib/II trial, 25 patients with previously untreated stage IV pancreatic cancer were treated with standard gemcitabine and nab-paclitaxel plus cisplatin at a dose of 25 mg/m2, 37.5 mg/m2, and 50 mg/m2 on days 1 and 8 of every 21-day cycle. Nine patients were enrolled in the phase Ib dose-escalation portion of the trial where 25 mg/m2 was established as the maximum-tolerated dose. Among 22 patients who started treatment at the recommended phase II dose of 25 mg/m2, 8 (36%) completed ≥6 cycles of treatment. Among the overall population, patients completed a median of 8 cycles of treatment (range, 1-15).
Eligible patients were ≥18 years of age, had histologically or cytologically confirmed measurable metastatic pancreatic ductal adenocarcinoma, a Karnofsky performance status score of 70% or higher, life expectancy of ≥12 weeks, and acceptable hematologic, hepatic, and renal function.
Patients had a median age of 65 years (range, 47-79). Approximately half (56%; n = 14) of patients were male, and the majority were white (96%; n = 24).
Notably, 16 (64%) patients were alive at 1 year, 10 (40%) at 2 years, 4 (16%) at 3 years, and 2 (8%) at over 4 years. Three patients were alive at the study conclusion. Median progression-free survival was 10.1 months (95% CI, 6.0-12.5), and the median overall survival was 16.4 months (95% CI, 10.2-25.3).
Tumor markers that had been collected at baseline indicated that 19 (76%) of 25 patients had high CA19-9 levels. Among 18 patients who were followed during treatment, 5 (28%) had CA19-9 levels that returned to normal, 8 (44%) had a decrease of ≥90%, and 16 (89%) had a decrease of ≥50%.
“In addition to a high overall response rate, this three-drug combination was well tolerated, with manageable side effects,” said principal study investigator, Gayle S. Jameson, MSN, ACNP-BC, AOCN, nurse practitioner and clinical research investigator at Scottsdale Healthcare.
The safety analysis included all 25 patients. The most common grade ≥3 treatment-related adverse events included thrombocytopenia (68%; n = 17), anemia (32%; n = 8), and neutropenia (24%; n = 6). Three fatalities were reported, 2 owing to study participation.
“Considering the rapid disease response, acceptable safety profile, and encouraging antitumor activity, further study of this triple-drug combination and additional tumor molecular analysis are needed to correlate these molecular findings with patient response to treatment,” Von Hoff stated in the press release.
As such, the regimen is also being explored in the neoadjuvant pancreatic cancer setting (NCT03138720) as well as in patients with advanced biliary cancers (NCT02392637).