STOCKHOLM – Prostate cancer patients with bone metastases may find relief from bone pain in a single infusion of ibandronate instead of standard single-dose palliative radiotherapy.
"Overall, there is no difference in the probability of pain relief after single-dose radiotherapy or single-infusion ibandronate [Boniva], with overall response rates of around 52%," Dr. Peter Hoskin said at the European Multidisciplinary Cancer Congress.
Prof. Peter Hoskin
He reported on the RIB (Single-Dose Local Radiation Therapy Compared With Ibandronate in Treating Patients With Localized Metastatic Bone Pain) trial involving 470 patients with prostate cancer or a raised prostate-specific antigen level of more than 100 ng/mL. Participants were evenly randomized to a single dose of 8 Gy local radiotherapy or a single 6-mg IV infusion of ibandronate. All patients were bisphosphonate free for at least 6 months, and roughly 90% were on androgen-deprivation therapy.
Patients provided details on analgesic use and rated their pain over the preceding 3 days using the Brief Pain Inventory (a categorical scale for worst pain, average pain, and least pain).
Pain response was measured using a combination of two different methods of analgesic score: a simple 3-point scale for analgesic strength based on the World Health Organization analgesic ladder, and an opioid equivalence calculated to give a single continuous variable based on the method described by Dr. Sebastiano Mercadante and colleagues.
The overall pain response rate was 51.3% at 4 weeks and 52.7% at 12 weeks, said Dr. Hoskin, a professor of clinical oncology at University College London and a radiation oncologist at Mount Vernon Cancer Centre in Northwood, England. There was no evidence of a treatment effect for change in pain relief from baseline at either 4 or 12 weeks when either pain criterion was used.
The mean change in the WHO response rate at 4 weeks was –3.7% and 6.7% at 12 weeks. The mean change in the Mercadante score was 4.4 units at 4 weeks and –1.5 units at 12 weeks. None of these differences was statistically significant.
At 4 weeks, more patients in the ibandronate group had worse Mercadante scores. This is consistent with more patients’ needing retreatment at 4 weeks after ibandronate; however, by 8 weeks, there was no overall advantage, Dr. Hoskin said. In all, 31% of patients receiving ibandronate and 24% of those receiving radiotherapy crossed over to the opposite treatment (P = .097).
Overall toxicity was the same in both treatment groups, with any toxicity reported in 38% of the ibandronate group and 40% of the radiotherapy group. As expected, the radiotherapy group experienced more diarrhea and nausea, whereas the ibandronate group experienced infusion-related events.
At a median follow-up of 11.6 months, overall median survival was identical at 12.2 months with radiotherapy and 12.8 months with ibandronate, Dr. Hoskin said at the joint congress of the European Cancer Organization (ECCO), the European Society for Medical Oncology (ESMO), and the European Society of Radiotherapy and Oncology (ESTRO).
An analysis of crossover patients revealed a significant improvement in survival in the group receiving ibandronate who crossed over to radiotherapy at 4 weeks. Median survival in this group was 16.8 months, compared with 12.7 months in the group crossing over from radiotherapy to ibandronate.
"Perhaps ultimately, as these studies progress and new studies are undertaken, combined treatment with radiotherapy and bisphosphonate may be optimal and show synergistic action," he said.
Invited discussant Dr. Daniel Zips of the National Center for Radiation Research in Oncology in Dresden, Germany, said that radiotherapy will remain the standard of care for most patients with localized bone pain resulting from metastases, but that ibandronate represents an effective treatment option for special clinical situations such as patients with contraindications to radiotherapy.
"The results of the crossover – and this might even be more important – suggest that radiotherapy or ibandronate represents a treatment option for patients who fail the first treatment," he added.
Given that only 50% overall responded to ibandronate or radiotherapy, Dr. Zips said that better, more effective therapies are clearly needed to improve the treatment of bone metastases.
RIB was sponsored by the Cancer Research UK and UCL Cancer Trials Centre. Dr. Hoskin disclosed no relevant conflicts of interest.