The US Food and Drug Administration (FDA) approved the drug olaratumab, an inhibitor of platelet-derived growth factor receptor alpha, for the treatment of patients with metastatic sarcoma when combined with the standard chemotherapy, doxorubicin. This is based on preclinical data showing that the combination of olaratumab plus doxorubicin was superior to doxorubicin or olaratumab alone. This resulted in the translation of these preclinical results into a randomized phase 2 study of doxorubicin at a dose of 75 mg/m2 given every 3 weeks for 8 cycles in combination with olaratumab at a dose of 15 mg/kg given on day 1 and day 8 of every 21-day cycle, compared with doxorubicin alone at the same dose of 75 mg/m2.
The results were quite impressive, with improvement in median overall survival from 14.7 months with doxorubicin alone to 26.5 months with a combination therapy given every 21 days. Median progression-free survival also improved from 4.1 to 6.6 months, with a slight increase in overall response rate from 11% to 18%. This study represents the first of its type to show that adding a second drug to doxorubicin—in this case, olaratumab—improves median overall survival.
There is also an impressive tail to the curve in the Kaplan-Meier plots. At 4 years, 40% of the patients were alive when given the combination of olaratumab and doxorubicin, compared with only 20% of patients with doxorubicin alone.
These results are based on a randomized phase 2 study with 133 patients. The study results are now undergoing a confirmatory randomized phase 3 study testing olaratumab and doxorubicin vs doxorubicin alone. The study has completed accrual, and long-term follow-up of these patients is ongoing. Hopefully, we will see the results in another year.
Because of the very compelling and exciting improvement in median overall survival that had not been seen before in the history of medical oncology for the treatment of patients with metastatic sarcoma, the US Food and Drug Administration (FDA) agreed to give this drug provisional approval. I believe that this drug will change the pattern of care for patients with this disease and offer them a new treatment option that will result in improvement in overall survival. Confirmatory results are forthcoming. We will have to wait to see whether these very impressive results will be validated in the second study.
We now have a new program, and we will see olaratumab become part of the standard of care for the treatment of metastatic sarcoma. It is a new day for patients with this disease, offering them a new hope and new treatment option for this very serious cancer.