Patients newly diagnosed with locally advanced pancreatic cancer who received induction therapy with nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) and gemcitabine achieved a time to treatment failure and median progression-free survival that exceeded the protocol-specified target by more than 2 months, investigators of the global phase II LAPACT trial reported at the 2018 Gastrointestinal Cancers Symposium.1
The combination of nab-paclitaxel and gemcitabine has promising antitumor activity.— Pascal Hammel, MD
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The median time to treatment failure was 8.8 months compared with the target of 6.6 months, based on historical precedent in patients with metastatic disease. 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, Clichy, France.
“The findings mirror those seen with nab-paclitaxel plus gemcitabine in the metastatic setting. In the phase III MPACT trial, this combination resulted in more than a threefold greater reduction in primary pancreatic tumor burden, vs gemcitabine,” Dr. Hammel said.
The National Comprehensive Cancer Network® (NCCN®) previously gave a qualified recommendation to the combination for locally advanced disease on the basis of the MPACT findings in metastatic disease.2 About 30% of patients with pancreatic cancer have unresectable locally advanced tumors at diagnosis, and for them, induction chemotherapy—with the hope of converting some of the tumors to resectable status—is the standard of care.
The LAPACT trial enrolled 107 patients with newly diagnosed, locally advanced pancreatic cancer, treating them with a planned number of 6 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 laparotomy to decide then whether surgical resection of the tumor was feasible. The study’s primary endpoint was time to treatment failure.
The final population included 61 patients who completed induction, after which 45 went on to receive investigator’s choice of therapy: 12 patients continued on nab-paclitaxel/gemcitabine, 17 received chemoradiation, and 16 went to surgery. For the entire population, the duration of chemotherapy treatment was 20.7 weeks; the median number of cycles was 5; approximately 75% of patients received the planned doses of nab-paclitaxel and gemcitabine. Dose reductions of each drug were necessary in about two-thirds of patients while there was no surprise about the safety comparing it to the MPACT trial.
Extended Time to Treatment Failure
The protocol-specified target for time to treatment failure was 6.6 months; after follow-up of up to 24 months, the median time to treatment failure reached 8.8 months, Dr. Hammel reported.
The induction therapy led to a partial response in 32.7% of the 107 patients in the intention-to-treat population. An additional 57.9% had stable disease for at least 16 weeks. The disease control rate at 16 weeks or later was 77.6%. Most patients experienced tumor reduction during treatment, and for almost
40% of patients, it was > 30%. In patients with paired measurements of serum CA 19-9, a reduction of ≥ 50% was observed in 75.3%, and 56.2% had ≥ 70% reduction.
Of the 16 patients who underwent surgical resection after induction therapy, 7 had clear surgical margins (R0 resection) and the remaining 9 had microscopic residual disease (R1). “Nab-paclitaxel plus gemcitabine induction allowed conversion to tumor resection in 15% of patients,” he reported. Median progression-free survival was 10.8 months for the entire cohort, and 72% of patients were alive at 1 year, he said.
“The combination of nab-paclitaxel and gemcitabine has promising antitumor activity,” Dr. Hammel concluded. “Induction therapy was tolerable and consistent with the known safety profile of the drugs. Quality of life was maintained in most patients.” ■
DISCLOSURE: Dr. Hammel has relevant relationships with Celgene, Shire, Ipsen, and Merck Serono.
1. Hammel P, Lacy J, Portales F, et al: Phase II LAPACT trial of nab-paclitaxel plus gemcitabine for patients with locally advanced pancreatic cancer. 2018 Gastrointestinal Cancers Symposium. Abstract 204. Presented January 19, 2018.
2. Von Hoff DD, Ervin T, Arena FP, et al: Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691-1703, 2013.
Brian M. Wolpin, MD, MPH
Invited discussant Brian M. Wolpin, MD, MPH, of Dana-Farber Cancer Institute in Boston, said the results of the LAPACT trial will be useful as an aid to patient counseling as well as in designing and interpreting future studies. However, he added, they are not...!-->!-->