SAN FRANCISCO — Time to treatment failure in newly diagnosed locally advanced pancreatic cancer exceeded historical standards in patients who received induction therapy with nab-paclitaxel (Abraxane) and gemcitabine, a preliminary trial showed.
The median time to treatment failure (TTF) was 8.8 months compared with the historical duration of 6.6 months. Median progression-free survival approached 1 year, and more than 70% of patients remained alive at 1 year, according to Pascal Hammel, MD, of Hopital Beaujon in Clichy, France, and colleagues.
The findings add to the combination’s activity in pancreatic cancer, following phase III results showing improved survival in association with a significant reduction in tumor burden among patients with metastatic pancreatic cancer, they reported here at the Gastrointestinal Cancers Symposium (GICS).
“The combination of nab-paclitaxel and gemcitabine has promising antitumor activity,” Hammel concluded. “Induction therapy was tolerable and consistent with the known safety profile of the drugs. Quality of life was maintained in most patients. The combination allowed conversion to tumor resection in 16 of 102 patients.”
The single-arm nature of the trial complicated interpretation of the results, said GICS invited discussant Brian M. Wolpin, MD, of Dana-Farber Cancer Institute in Boston. Clinicians can use the results as an aid to patient counseling, and the trial provided data useful for the design and interpretation of future studies.
“These results are unlikely to change clinical practice,” said Wolpin. “Many patients with locally advanced pancreatic cancer already receive multiagent chemotherapy. The study was not designed to definitively demonstrate improvement in patient outcomes. The optimal treatment approach for locally advanced pancreatic cancer remains unclear.”
The rationale for the trial, known as LAPACT, came from recognition that 30% of patients with pancreatic cancer have unresectable locally advanced tumors at diagnosis. Induction chemotherapy is standard for patients in this clinically setting, Hammel noted.
The previously reported success of the combination in patients with metastatic pancreatic cancer suggested potential efficacy of nab-paclitaxel and gemcitabine for locally advanced disease. The National Comprehensive Cancer Network previously gave a qualified recommendation to the combination for locally advanced disease on the basis of the trial in the metastatic setting, Hammel stated.
Investigators in the LAPACT trial enrolled 107 patients with newly diagnosed, locally advanced pancreatic cancer. The patients received a maximum of six cycles of induction therapy with nab-paclitaxel and gemcitabine. Investigators then had the option to continue the combination, treat patients with chemoradiation, or proceed to surgical resection.
All but one patient started induction therapy, and 61 of them completed the planned therapy. Subsequently, 12 patients continued the combination, 17 had chemoradiation, and 16 underwent surgical resection. The remaining 16 did not receive investigator’s choice of treatment after induction.
The protocol-specified standard for time to treatment failure was 6.6 weeks. After follow-up for as long as 24 months, the cohort had a median TTF of 8.8 weeks (90% CI 6.67-9.82).
The induction therapy led to partial response in 35 (32.7%) of 107 patients in the intention-to-treat population. An additional 62 (57.9%) patients had stable disease of at least 16 weeks. The disease control rate (response plus stable disease) was 77.6% if stable disease were defined as ≥16 weeks and 65.4% if defined as ≥24 weeks. Hammel said 38.2% of patients had a reduction in tumor size >30%, most patients had some tumor reduction during induction therapy.
In patients with paired measurements of serum CA19-9, 75.3% had at least a 50% reduction in the cancer antigen, and 56.2% had at least a 70% reduction.
Of the 16 patients who underwent surgical resection after induction therapy, seven had clear surgical margins (R0) and the remaining nine had microscopic residual disease (R1).
The study was supported by Celgene.
Hammel disclosed relevant relationships with Celgene, Shire, Ipsen, and Merck Serono.