In the phase III HALO 109-301 trial reported in the Journal of Clinical Oncology, Eric Van Cutsem, MD, PhD, and colleagues found that the addition of pegvorhyaluronidase alfa (PEGPH20) to nab-paclitaxel plus gemcitabine (AG) did not improve overall survival or progression-free survival in patients with previously untreated, hyaluronan-high, metastatic pancreatic ductal adenocarcinoma.
Eric Van Cutsem, MD, PhD
Study Details
In the international double-blind trial, 492 patients (intent-to-treat population) were randomly assigned 2:1 between March 2016 and December 2018 to receive PEGPH20 plus AG (n = 327) or placebo plus AG (n = 165). Treatment was given intravenously in 4-week cycles (3 weeks on, 1 week off) until disease progression or intolerable toxicity. Treatment consisted of PEGPH20 at 3.0 mg/kg twice per week in cycle 1 and once per week thereafter, nab-paclitaxel at 125 mg/m2 once per week, and gemcitabine at 1,000 mg/m2 once per week. The primary endpoint was overall survival in the intent-to-treat population.
Overall Survival
At data cutoff in May 2019, median overall survival was 11.2 months (95% confidence interval [CI] = 10.3–12.3 months) in the PEGPH20 plus AG group vs 11.5 months (95% CI = 9.0–12.5 months) in the placebo plus AG group (hazard ratio [HR] = 1.00, 95% CI = 0.80–1.27, P = .97).
In a supportive analysis with longer follow-up (data cutoff in September 2019), median overall survival was 11.4 vs 11.7 months (HR = 1.02, 95% CI = 0.82–1.27, P = .85).
Median progression-free survival was 7.1 months (95% CI = 5.5–7.4 months) vs 7.1 months (4.8–8.3 months; HR = 0.97, 95% CI = 0.75–1.26). Use of subsequent therapies after treatment discontinuation was similar in the two treatment groups. Objective response was observed in 47% vs 36% of patients (response ratio = 1.29, 95% CI = 1.03–1.63). Median duration of response was 6.1 vs 7.4 months.
KEY POINTS
- Median overall survival was 11.2 vs 11.5 months.
- Median progression-free survival was 7.1 months vs 7.1 months.
Adverse Events
Grade ≥ 3 adverse events with a 2% or higher incidence in the PEGPH20 plus AG group included fatigue (16.0% vs 9.6%), muscle spasms (6.5% vs 0.6%), and hyponatremia (8.0% vs 3.8%). Adverse events led to discontinuation of treatment in 28.9% vs 28.8% of patients, with causes including fatigue (2.8% vs 0.6%), musculoskeletal events (2.8% vs 0%), and gastrointestinal disorders (3.4% vs 1.3%). Adverse events led to death in 5.8% vs 4.5% of patients, with causes including gastrointestinal bleeding (0.9% vs 0%).
The investigators concluded, “The addition of PEGPH20 to AG increased the objective response rate but did not improve overall survival or progression-free survival. The safety profile of PEGPH20 plus AG was consistent with that found in previous studies. These results do not support additional development of PEGPH20 in metastatic pancreatic ductal adenocarcinoma.”
Margaret A. Tempero, MD, of the Division of Hematology and Oncology, UCSF Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Halozyme Therapeutics, Inc. For full disclosures of the study authors, visit ascopubs.org.
