Insights From: Victor Villalobos, MD, PhD, University of Colorado School of Medicine; Saketh Guntupalli, MD, University of Colorado School of Medicine; Shreyaskumar R. Patel, MD, University of Texas MD Anderson Cancer Center; Anthony P. Conley, MD, University of Texas MD Anderson Cancer Center
Anthony P. Conley, MD: Traditionally, the treatment of advanced metastatic sarcoma involved the use of medicines such as doxorubicin, either alone or in combination with other agents. Or, sometimes, medicines such as gemcitabine in combination with docetaxel. Within the last year, we have a new drug that’s been approved. This is a humanized monoclonal antibody, PDGFR-alpha, known as olaratumab. This particular medicine was FDA approved for patients with advanced metastatic sarcoma for which you would consider doxorubicin-based therapies. The nice addition of this particular medication is that the side effect profile is favorable compared to many other types of therapies that we often combine with doxorubicin.
Prior to the approval of olaratumab, we oftentimes either used doxorubicin by itself to treat advanced metastatic disease. We would sometimes pair doxorubicin with other medicines, such as ifosfamide, or, sometimes lesser known medicines, such as dacarbazine. While these combinations have been used for years, none of these combinations have successfully shown survival advantages. With the approval of olaratumab, we now have a second agent that we can use (for which there is survival data). This particular medicine was FDA approved for use in patients in whom you would consider doxorubicin. This particular medicine not only was associated with a higher response rate, but it also had a much higher progression-free survival and a much higher overall survival in a phase I/phase II setting.
In interpreting this data, it’s important to know that there is a phase III clinical trial. It has completed, and we’re awaiting final results. But at this time, we do have the available use of olaratumab. Because of its side effect profile, it has added to our ability to treat patients. Importantly, patients do sometimes experience more nausea and neutropenia with this particular medicine. But the febrile neutropenia rate between the combination of doxorubicin plus olaratumab was essentially the same as single-agent doxorubicin. This is important because febrile neutropenia oftentimes can be a scary experience for the patient. And, it can be a very serious concern for the clinician.
The clinical trials that led to the approval of olaratumab in combination with doxorubicin featured several different subtypes of sarcomas. Importantly, these trials were weighted as such to provide emphasis on diseases such as leiomyosarcoma, liposarcoma, and other variants such as undifferentiated pleomorphic sarcoma.
Within the phase I/phase II trial evaluating olaratumab in combination with doxorubicin, as compared to doxorubicin alone, leiomyosarcoma was the most common subtype tested. Based on this, I think it’s safe to say that the best available data is in patients with leiomyosarcoma. Because of this, I do recommend this combination—particularly in patients in whom we want to consider doxorubicin-based therapies.
I’ve had patients that take the combination, complete the 6 cycles of combination therapy, and are then able to go on to maintenance olaratumab with great success. In these patients, I often see an improvement of symptoms, reduction of tumor size, and overall improvement of quality of life.
In one instance, I had a 78-year-old patient who was actually in great health. For this patient, I considered doxorubicin in combination with olaratumab. The concern that we had was that his age and comorbidities could likely impact his ability to tolerate these medicines. But we found that when treating this patient with the combination, the patient tolerated the therapy very well. The patient had a response, early on. His side effects, which were few, such as neutropenia, were managed well. He never had any hospitalizations for febrile neutropenia, which was important. And, he was able to complete all 6 cycles of the combination therapy. He then went on to have maintenance therapy for, essentially, 7 months more. He had a very good quality of life during that particular time point.