Notable Results with Regorafenib in Treating Stage 4 Osteosarcoma (Bone Cancer)

The Lancet Oncologypublished a phase II clinical trialin which Duffaud and colleagues presented evidence in patients with progressive cancer despite prior treatment, with metastatic osteosarcoma(bone cancer), an adult patient group, that the drug regorafenib (Stivarga) was effective.

This noncomparative, double-blind study includes 4 groups of patients diagnosed with osteosarcoma, Ewing sarcoma, chondrosarcoma or chordoma. The current report presents findings from the osteosarcoma group.

Note: Osteosarcomas (bone cancer), are among rare cancers. However, in the 15 - 19 age group, this is the 5th most common cancer. Effective chemotherapy has dramatically increased survival in patients with osteosarcoma. Chemotherapy can achieve local disease control reaching %80 - 90. Nevertheless, unlike other cancers, osteosarcomas are known to metastasize to other organs much earlier. These metastases are responsible for most deaths from this disease.

Details of the Study

For stage 4 osteosarcoma, after 1 or 2 prior lines of chemotherapy and disease progression, from 13 different French hospitals between 2014 - 2017, 38 adult patients were assigned to receive daily regorafenib at 160 mg or placebo , in two arms at a 2 to 1 ratio. In each 28-day period, patients took these drugs as tablets for 21 days, and patients in both groups also received best supportive care.

The primary endpoint the study sought to measure was the proportion of patients without cancer progression at the end of 8 weeks. Patients in the placebo group were allowed to receive regorafenib after cancer progression. The results represent the final analysis of the osteosarcoma group; studies of the other cohorts (Ewing sarcoma, chondrosarcoma or chordoma) are ongoing.

Study Results

In the regorafenib group, among 26 patients, 17 (% 65) had no progression at 8 weeks, compared with, among 12 patients in the placebo group, 0 (% 0). In the regorafenib group, 2 patients had partial responses, lasting 6.2 and 12.9 months. In contrast, no patients responded in the placebo group. Median progression-free survival was 16.4 weeks versus 4.1 weeks.

Adverse Effects

Among those receiving regorafenib, % 24 experienced serious treatment-related adverse effects , while no serious adverse effects occurred in those receiving placebo. During treatment, the most common severe (grade ≥3) adverse effects with regorafenib were hypertension (%24), hand-foot skin reaction (%10), fatigue (%10), hypophosphatemia [low blood phosphate] (%10) and chest pain (%10). No treatment-related deaths occurred.

Conclusion

In conclusion, this study strongly suggests that regorafenib has clinically meaningful antitumor activity and a favorable effect in delaying disease progression in adult patients with recurrent, progressive, metastatic osteosarcoma after conventional chemotherapy. Regorafenib may also be considered in metastatic osteosarcoma and potentially earlier in the disease course for patients at high risk of recurrence. In this respect, we consider it highly likely that regorafenib will receive approval for treating osteosarcoma in the near future.