Adding a platinum to standard gemcitabine and nab-paclitaxel led to impressive responses and overall survival rates in a small pilot trial in patients with stage IV pancreatic cancer.
Gayle Jameson, MSN, ACNP-BC, AOCN
Adding a platinum to standard gemcitabine and nab-paclitaxel led to impressive responses and overall survival (OS) rates in a small pilot trial in patients with stage IV pancreatic cancer.1
With 11 of 25 patients in the study still alive, the median OS is 16.5 months, said Gayle Jameson, MSN, ACNP-BC, AOCN, when presenting the findings at the 2017 Gastrointestinal Cancers Symposium held in San Francisco. “We have not seen that in stage IV pancreatic cancer to date. It’s a very small study though,” she said. “The median survival will continue [to increase] because the data are not mature and we still have 11 patients alive.”
The genomes of patients with metastatic pancreatic cancer contain myriad intrachromosomal aberrations, indicating a high prevalence of DNA repair deficiencies. In the phase II Stand Up 2 Cancer trial, every patient with pancreatic ductal adenocarcinoma had multiple interstitial copy number aberrations,2noted Jameson, nurse practitioner and associate investigator of Clinical Trials, HonorHealth Research Institute, Scottsdale Healthcare Research Institute. “These types of tumors are very sensitive to platinums, which are DNA-damaging agents,” she said.
Twenty-five patients with stage IV adenocarcinoma of the pancreas, no prior chemotherapy for systemic disease, Karnofsky performance status (KPS) ≥70%; life expectancy ≥12 weeks, and measurable disease were enrolled at 3 US sites between December 2013 and July 2016. Nab-paclitaxel was administered at 125 mg/m2undiluted, gemcitabine at 1000 mg/m2, each infused over 30 minutes on days 1 and 8 of a 21-day cycle. In addition, patients received either 25 mg/m2of cisplatin infused over 60 minutes, escalated to 50 mg/m2, after the nab-paclitaxel infusion.
Median age of the patients was 65 years, all had KPS ≥80%, and 79% had an elevated CA19-9 at baseline. Primary tumor location was the head of the pancreas in 24%, body in 32%, and tail in 24%. Twenty percent had their tumor resected.
The maximum tolerated and phase II dose of cisplatin was 25 mg/m2. “It’s a very low dose of cisplatin, but adding that we’ve seen a very impressive response rate,” she said.
The overall response rate (ORR) by RECIST v1.1 criteria was 71%, with 2 complete responses (8.3%) and 15 partial responses (62.5%). The 71% ORR is “exceptional in stage IV pancreas disease,” Jameson indicated. Most patients who had an abnormal level of CA19-9 at baseline had values decline by 50% to 100% within 90 days.
Eighteen of the 25 patients had a ≥30% reduction in tumor size from baseline, and 3 of the 25 had a resolution of measurable tumor by RECIST criteria.
The median survival to date of 16.5 months “has not been seen in stage IV pancreatic cancer,” she said. Some 64% of patients were alive at 12 months, 20% were alive at 24 months, 4% were still alive at 36 months, with 11 of the 25 patients still alive at last follow-up.
The most common drug-related grade ≥3 adverse events were thrombocytopenia (76% total; grade 3, 36%; grade 4, 40%) with no serious bleeding events, anemia in 32% (all grade 3), neutropenia in 24% (grade 3, 20%; grade 4, 4%), infection in 20% (grade 3, 16%; grade 4, 4%), and grade 3 diarrhea in 16%.
“We’d like to expand the study but we also have a tissue analysis that’s upcoming,” said Jameson. “As we look for genomic signatures of response, this is going to be key.” A study examining this triplet in the neoadjuvant setting is also planned.