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Second-Line Treatment Feasible, Beneficial After Upfront Nab-Paclitaxel in Pancreatic Cancer

Published: Tuesday, Feb 02, 2016

David Goldstein, MD

David Goldstein, MD

Second-line treatment of metastatic pancreatic cancer proved to be feasible and beneficial, particularly for patients who received nab-paclitaxel in addition to gemcitabine in the first-line setting, according to extension data from a phase III trial.

Patients who received any second-line therapy after progression had a median total overall survival (OS) of 12.8 months if their initial treatment was nab-paclitaxel and gemcitabine compared with 9.9 months if they received gemcitabine alone in first-line.1 Second-line treatment containing 5-FU or capecitabine was associated with a median total survival of 13.5 months after first-line nab-paclitaxel and gemcitabine versus 9.5 months with gemcitabine monotherapy.

Patients who received second-line FOLFIRINOX after first-line nab-paclitaxel and gemcitabine had the longest total survival, a median of 15.7 months, as reported at the 2016 Gastrointestinal Cancers Symposium.

“The take-home message from this analysis is that second-line therapy for metastatic pancreatic cancer is feasible, and patients benefit from it,” said David Goldstein, MD, a medical oncologist at Prince of Wales Hospital in Sydney, Australia. “Until now, second-line therapy for metastatic pancreatic cancer has received little consideration.”

“The keys to successful second-line treatment are patient selection—patients who are otherwise in good condition—and selection of appropriate regimens for second-line,” he added.

Use of second-line therapy in metastatic pancreatic cancer has remained limited for unclear reasons. The aggressive nature of the disease is a possible contributing factor, but first-line therapies that have improved efficacy might encourage use of second-line treatment in a larger proportion of patients, Goldstein noted.

Gemcitabine has an established role in first-line treatment of patients with metastatic pancreatic cancer. More recently, nab-paclitaxel has been integrated as an addition to gemcitabine in the first-line setting. Analysis of nab-paclitaxel’s performance in first-line treatment can inform treatment planning, including consideration of second-line therapy.

Goldstein and colleagues performed a posthoc analysis of the randomized phase III MPACT trial, which evaluated first-line treatment of metastatic pancreatic cancer with gemcitabine alone or in combination with nab-paclitaxel. When the randomized treatment ended in 2013, an extension study was initiated to accumulate additional information about survival and clinical management, including second-line treatment for metastatic pancreatic cancer.

The primary objectives of the analysis of data from the extension phase were total OS from initial randomization and OS-2, defined as survival from the end of first-line therapy. About 40% of patients in the MPACT trial received second-line therapy, which included 5-FU or capecitabine in more than 75% of cases.

Patients who received second-line therapy had better baseline performance status, and patients who received FOLFIRINOX in second-line had better performance status at the end of first-line treatment.

During the randomized phase of the trial, 431 patients received nab-paclitaxel and gemcitabine and 430 received gemcitabine alone. In the extension study, 170 in the nab-paclitaxel arm received second-line therapy, as did 177 patients randomized to gemcitabine alone.

Among patients who received second-line therapy, 59% and 74% of those from the nab-paclitaxel and gemcitabine monotherapy arms, respectively, discontinued first-line therapy because of progression, and 26% and 14% discontinued because of adverse events.

Initial treatment with nab-paclitaxel was associated with significantly longer total survival among patients who received second-line therapy (P = .015) and those who did not (6.2 vs 4.7 months; P <.001). OS-2 was similar in the nab-paclitaxel and gemcitabine groups among patients who received second-line therapy (6.7 vs 6.4 months; P = .273) but was significantly longer with nab-paclitaxel among patients who did not receive second-line therapy (2.5 vs 1.6 months; P <.001).

A second study focused on the effectiveness and resource utilization associated with first-line treatment of metastatic pancreatic cancer with the combination of nab-paclitaxel and gemcitabine or FOLFIRINOX, which demonstrated superiority versus gemcitabine monotherapy in the phase III ACCORD trial.2 Investigators performed a retrospective cohort study, using data from an electronic medical record platform involving patients throughout the United States.

Such an analysis would provide real-world data to support decision making, including sequencing, in an era of expanding second-line options, Fadi S. Braiteh, MD, a medical oncologist at the University of Nevada-Las Vegas, and colleagues noted in a poster presentation during the meeting.

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