A single dose of radiotherapy and a single injection of ibandronate provided similar pain relief from bone metastases in men with metastatic prostate cancer, according to results of the first large randomized phase III trial of a bisphosphonate drug in this setting. No preferential response was seen for either treatment; only about 52% of patients in each arm of the prospective, randomized RIB study had a good overall response.
“Toxicity was similar with radiotherapy and ibandronate, but survival is improved with both treatments,” said Peter Hoskin, MD, of Mount Vernon Cancer Centre in Northwood, United Kingdom, who presented these results during the 2011 European Multidisciplinary Cancer Congress.
“It is important to emphasize that radiotherapy still has a critical role to play [in this setting], and it is a highly effective treatment for many cancer patients,” Hoskin said. “Radiotherapy remains the treatment of choice for patients with solitary metastases, pathological fracture, and neurological complications of bone metastases. Ibandronate adds to the arsenal of available treatments, and we believe the findings can be applicable to other cancers that spread to the bone.”
RIB randomized 470 men with primary prostate cancer and painful bone metastases to receive either a single dose of 8 Gy of localized radiation or a single 6-mg intravenous dose of ibandronate. Patients reported their pain score based on the Brief Pain Inventory, a 10-point scale ranging from no pain (0) to severe pain (10), and detailed their analgesic use at baseline and then at 4, 8, 12, 26, and 52 weeks after treatment. At 4 weeks, nonresponders were allowed to cross over to the other arm. The primary endpoint was pain relief at weeks 4 and 12 compared with baseline.
The patients’ median age was 73 years, and more than 90% were on androgen-deprivation therapy. The median time from prostate cancer diagnosis was 2 years. At 4 weeks, overall response rate (ORR) was 53% for radiotherapy versus 49% for ibandronate; at 12 weeks, ORR rate was 49% versus 56%, respectively. The percentage of crossovers was 24% for radiotherapy and 31% for ibandronate. Median survival was 11.8 months for those treated only with radiotherapy and 11.4 months for those treated only with ibandronate. For patients who crossed over from radiotherapy to ibandronate, median survival was 12.7 months versus 16.8 months for those treated with ibandronate who then crossed over to radiotherapy.
Few side effects were reported. The most common symptoms with radiotherapy, if it was near the abdomen, were transient nausea and gastrointestinal upset; flu-like symptoms were the most common adverse event with ibandronate.
These results suggest that perhaps these treatments could be combined, but optimal timing and the sequence of radiotherapy and ibandronate remain to be defined, said Hoskin.
Daniel Zips, MD, of Technical University in Dresden, Germany, said: “This is the first large randomized trial to compare radiotherapy versus a bisphosphonate in the treatment of metastatic bone pain. Up to 75% of men with advanced disease will develop bone metastases. Androgendeprivation therapy has negative effects on bone mineral density, and the complications of bone metastases have an impact on quality of life and possibly survival.”
Zips said that this trial was designed as an equivalence trial, and the major finding was equivalence for pain relief.