ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.
Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.
"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."
The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.
Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.
Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.
There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.
In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).
The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.
Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.
Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.
In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.
The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.
Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.
Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.