Response Rates Improved With Platinum Added to Nab-Paclitaxel/Gemcitabine in Advanced Pancreatic Cancer

Author(s):

The addition of a platinum agent to standard gemcitabine and nab-paclitaxel was found to be associated with impressive response and overall survival rates in patients with stage IV pancreatic cancer.

Gayle Jameson, MSN,

ACNP-BC, AOCN

The addition of a platinum agent to standard gemcitabine and nab-paclitaxel was found to be associated with impressive response and overall survival (OS) rates in patients with stage IV pancreatic cancer, according to findings of a small pilot trial presented at the 2017 Gastrointestinal Cancers Symposium.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 meeting. “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,² noted 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/m2 undiluted, 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/m2 of 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.

References

Jameson GS, Borazanci E, Babiker HM, et al. A phase Ib/II pilot trial with nab-paclitaxel plus gemcitabine plus cisplatin in patients (pts) with stage IV pancreatic cancer. Presented at: 2017 Gastrointestinal Cancers Symposium; January 19-21, 2017; San Francisco, CA. Abstract 341.
Barrett MT, Lenkiewicz, Evers L, et al. Abstract 3697: phase II study of therapy selected by molecular profiling in patients with previously treated metastatic pancreatic cancer — SU2C-001. Cancer Res. 2012;72(8 suppl):abstr 3697. doi:10.1158/1538-7445.AM2012-3697.