More Data Needed on Satraplatin for Prostate Cancer

Zosia Chustecka

July 25, 2007

July 25, 2007 -- The experimental drug satraplatin ( Orplanta, GPC Biotech Inc) could offer a new option to men with hormone-refractory prostate cancer, but it now looks unlikely to be available soon. Yesterday the Food and Drug Administration's (FDA's) Oncology Drug Advisory Committee (ODAC) voted 15-0 to recommend that the agency delay approval of the drug until there are data on overall survival (OS). The FDA is not bound to follow the advice of its advisory committees but usually does so.

The committee was reviewing data from a large company-sponsored phase 3 trial, known as Satraplatin and Prednisone Against Refractory Cancer (SPARC). The sponsor's results so far show a statistically significant effect on progression-free survival (PFS), as well as on several other end points, including time to pain progression. But it appears that these were judged insufficient, as the ODAC recommended waiting until data on OS become available, which may not be until the end of 2007.

Details of the SPARC trial, as presented by the manufacturer to the ODAC, are now available on the FDA website, but the results were reported for the first time at the American Society for Clinical Oncology 43rd Annual Meeting in Chicago. The ASCO presentation was made by Cora Sternberg, MD, from the San Camillo Forlanini Hospital, in Rome, Italy, who commented that satraplatin, if approved, would offer a new oral treatment for second-line therapy in patients with metastatic hormone-refractory prostate cancer.

In the ASCO report of the trial, 950 such patients were enrolled, all of whom had progressed after first-line chemotherapy (about half had received docetaxel); nearly 70% of patients were older than 65 years of age (27% were older than 75 years). More than a third of patients reported more severe degrees of pain, but almost half had minimal or no pain. Patients were randomized 2:1 to receive either satraplatin (80 mg/m 2 per day for 5 days every 5 weeks) with prednisone or placebo plus prednisone. The study design included two co-primary end points, OS and PFS. PFS in this study was a composite end point of radiological progression, symptomatic progression, skeletal events, or death. Symptomatic progression also had subcomponents.

The satraplatin-plus-prednisone group showed a significant 42% improvement in the composite PFS end point, with a median PFS of 16 weeks compared with 6 weeks with prednisone alone (hazard ratio [HR], 0.58; P = .023). The drug also had a significant effect on secondary end points, Dr. Sternberg reported. It increased the time to pain progression, the pain response rate, the tumor response rate, and the prostate-specific-antigen (PSA) response rate compared with the control group.

The most common adverse effect was myelosuppression, with grade 3/4 neutropenia seen in 21.1% of patients in the satraplatin-plus-prednisone cohort compared with 0.6% with prednisone alone ( P < .001), Dr. Sternberg reported. Gastrointestinal disorders were the most frequent nonhematological adverse events (occurring in 57.9% of the patients receiving satraplatin), the manufacturer noted in a press release issued at the time. Eight percent of patients in the satraplatin group experienced grade 3 or 4 gastrointestinal toxicities, including nausea (1.3%), vomiting (1.6%), diarrhea (2.1%), and constipation (2.1%). In addition, 5% or fewer of patients in the satraplatin group experienced grade 3 or 4 fatigue (1.7%), grade 3 or 4 infections (4.0%), or pulmonary/respiratory grade 3 or 4 toxicities (3.0%).

Discussing the trial at the ASCO meeting, Ian Tannock, MD, PhD, from Princess Margaret Hospital, in Toronto, Ontario, commented that it was difficult to place this trial into context, as there is no FDA-approved therapy for use second line in metastatic hormone-refractory prostate cancer, although various chemotherapy agents are used in practice. He suggested that it would have better to have used 1 of these chemotherapy agents as the comparator instead of prednisone, as he would not imagine that in practice a patient who was fit enough to receive chemotherapy would have been treated with prednisone alone.

An oncologist present at yesterday's ODAC meeting told Medscape that there was some concern among the committee members about the composite PFS end point created by the sponsor, as it was complex and some of the data were not well documented. The committee was not satisfied with the strength of the evidence presented and also observed that relief of pain, 1 of the claims for benefit from satraplatin, could be obtained from the use of a narcotic analgesic, which would carry less risk of toxicity than a chemotherapy agent.

GPC-Biotech, the company developing satraplatin, said that it was "extremely disappointed with the decision." Chief executive officer Bernd Seizinger, MD, PhD, said in a company broadcast: "We continue to believe in the strength of the data from the SPARC trial and believe that satraplatin can make a real difference to patients with prostate cancer."

Data on overall survival should be available in about 6 months, the company said, adding that it has sufficient funds to get to this end point. In a slide presentation at the ODAC meeting, company chief medical officer Marcel Rosenzweig, MD, noted that an interim overall survival analysis, carried out after 463 deaths were recorded, favors the satraplatin group, with a hazard ratio of 0.90 (95% CI, 0.74 - 1.09). The final analysis for overall survival will be made after the prespecified number of 700 deaths are recorded, and while it is difficult to predict exactly when this will be, the company estimated that this point may be reached in 6 months. After submitting those data, the company estimated that it might take another year to gain approval, which would bring the drug onto the market at the end of 2008.

American Society for Clinical Oncology 43rd Annual Meeting: Abstract 5019. Presented June 4, 2007.

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