Nab-Paclitaxel/Gemcitabine Induces Encouraging Responses in Locally Advanced Pancreatic Cancer

Pascal Hammel, MD, PhD

Pascal Hammel, MD, PhD

In patients with newly diagnosed locally advanced pancreatic cancer, induction treatment with nab-paclitaxel (Abraxane) plus gemcitabine induced an overall disease control rate (DCR) of 77.6%, according to updated findings from the phase II LAPACT trial presented at the 2018 Gastrointestinal Cancers Symposium.

In the single-arm, international trial, the nab-paclitaxel regimen elicited an objective response rate of 32%. The overall disease control rate (DCR) was 77.6%. The median progression-free survival was 10.8 months (90% CI, 9.26-11.63) with the combination and the 12-month overall survival rate was 72% (90% CI, 64.5%-78.9%). The time to treatment failure (TTF) was 8.8 months (90% CI, 6.67-9.82)

“Disease control is key in our patients with locally advanced disease, as it may lead to opportunities for additional treatment interventions, including radiotherapy, or even, in some favorable cases, surgical resection," lead study author Pascal Hammel, MD, PhD, Gastroenterologist/Oncologist, Hôpital Beaujon, Clichy France, said in a statement. "The results from this study are encouraging, as it shows that induction therapy has the potential to help us achieve disease control in these locally advanced patients.”

The study enrolled 106 patients at a median age of 65 years with locally advanced pancreatic cancer. Induction therapy was administered with nab-paclitaxel at 125 mg/m²plus gemcitabine at 1000 mg/m²on days 1, 8, and 15 of a 28-day cycle for 6 total cycles. All patients had not received prior therapy for pancreatic cancer and were classified as unresectable. Following the induction phase, patients were offered continuation of nab-paclitaxel/gemcitabine or a switch to another treatment.

The primary endpoint of the study was TTF, with a goal of achieving a median of 6.6 months. All responses in the study were partial responses. The stable disease (SD) rate for ≥16 weeks was 44.9% and 32.7% of patients had stable disease for ≥24 weeks. The ≥16 week DCR was 77.6% and the ≥24 week DCR was 65.4%.

All 6 cycles of induction therapy were completed by 57.5% of patients in the trial. Overall, 15% of patients went on to subsequent surgical resection following treatment with the regimen. Those who completed induction but did not receive surgery went on to chemoradiation (16%) or continued nab-paclitaxel and gemcitabine (11%).

Of those who did not complete induction therapy, the most common causes for treatment discontinuation were adverse events (n = 20), progressive disease (n = 8), protocol non-compliance (n = 5), physician decision (n = 6), death (n = 2), and other reasons (n = 4).

The most frequently observed grade ≥3 treatment-emergent adverse events were neutropenia (42%), anemia (11%), fatigue (10%), thrombocytopenia (7.5%), peripheral sensory neuropathy (3.8%), diarrhea (3.8%), and febrile neutropenia (3.8%).

“Pancreatic cancer remains an extremely challenging disease to treat because it is often diagnosed at the metastatic stage, and even those diagnosed with locally advanced disease typically have a poor prognosis,” noted Hammel.

The combination of nab-paclitaxel and gemcitabine was approved for patients with metastatic pancreatic cancer in 2013, based on findings from the phase III MPACT trial. In this trial, the median overall survival was 8.5 months with nab-paclitaxel plus gemcitabine compared with 6.7 months for patients treated with gemcitabine alone (HR, 0.72; 95% CI, 0.62-0.84;P<.0001).

&ldquo;Since its approval to treat metastatic pancreatic cancer in 2013, the Abraxane plus gemcitabine regimen has become a standard of care in first-line metastatic pancreatic cancer,&rdquo; Nadim Ahmed, president, Hematology and Oncology for Celgene, the company developing the regimen, said in a statement. &ldquo;The findings from LAPACT offer insight into the potential of Abraxane-based treatment for locally advanced pancreatic cancer patients and it&rsquo;s encouraging to see a nearly 9-month time to treatment failure in these patients treated with an Abraxane regimen.&rdquo;

Several trials continue to assess nab-paclitaxel for patients with pancreatic cancer. In this setting, the agent is being explored in combination with more than 50 other agents across 130 clinical trials, according to Celgene. Most notably, the phase III APACT trial exploring adjuvant nab-paclitaxel/gemcitabine compared with gemcitabine alone recently completed enrollment of 866 participants. Initial findings from this open-label trial are anticipated in early 2019 (NCT01964430).

Reference:

Hammel P, Lacy J, Portales F, et al. Phase II LAPACT trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC).J Clin Oncol.2018;36 (suppl 4S; abstr 204).