William K. Oh, MD
The optimal sequence of treatments for patients with metastatic castration-resistant prostate cancer (mCRPC) is still unclear, especially after a retrospective study assessed the real-world outcomes in patients with mCRPC receiving second-line chemotherapy versus alternative androgen receptor (AR)–targeted agents after a lack of response to frontline AR-targeted therapies.
Using Altos electronic medical records, 345 patients with mCRPC who did not respond to first-line AR-targeted agents and either second-line chemotherapy or AR-targeted agents were studied. Outcomes were evaluated from the start of second-line treatment. Patients who received second-line chemotherapy versus AR-targeted agents had a median age of 74 versus 79, respectively, as well as a worse prognosis with a higher prostate-specific antigen (PSA) of 439 versus 231, respectively. Additionally, patients in the chemotherapy arm had a PSA response (adjusted odds ratio, 2.27; P
= .005), and there was a non-statistically significant trend towards improved overall survival (OS) for second-line chemotherapy versus an AR-targeted agent. The findings suggest that treatment with second-line chemotherapy versus second-line AR-targeted agents may be beneficial for patients who previously had little to no response to frontline AR-targeted agents.
“It suggests that not only should those patients not receive a second AR-targeted therapy if they didn't respond particularly well to the first, but that they may have a survival benefit if they receive chemotherapy instead,” explained lead study author William K. Oh, MD.
In an interview with OncLive
during the 2017 Genitourinary Cancers Symposium, Oh, who is chief of the Division of Hematology and Medical Oncology, and professor of Medicine and Urology at Mount Sinai School of Medicine, discussed the continued use of chemotherapy in patients with mCRPC.
OncLive: Can you provide an overview of the study and the rationale for it?
One of the issues about the sequence of new therapies for CRPC is that we don’t know if or when the patient should receive chemotherapy in relation to AR-targeted therapies—or, when they should receive radium-223 dichloride (Xofigo) and other treatments. We were interested in looking at this question by using real-world data from a large electronic medical records system.
Here, we looked at 4000 men who had received chemotherapy or AR-targeted therapy for prostate cancer. What we were really interested in was second-line therapy. These were patients who had received first-line AR-targeted therapy and had a very short duration of response. They were primarily resistant to AR-targeted therapy and we looked at the outcomes based on whether they received second-line chemotherapy or a second AR-targeted agent.
What do the results of this study mean for patients with prostate cancer who have a poor prognosis?
What we found in our study was that patients who had received chemotherapy after first-line AR-targeted therapy seemed to do better. These were patients who were intrinsically sicker, younger, had worse prognostic factors, their hemoglobin levels were lower, and their lactate dehydrogenase (LDH) levels and alkaline phosphates were higher. These were patients for whom the treating oncologist thought needed more aggressive treatment and they received chemotherapy.
The other group of patients who received second AR-targeted therapy were generally a little older and had better prognostic features. Despite this, when adjusting for those prognostic features, patients who received chemotherapy seemed to have a trend toward improved survival.
When we looked at a subset analysis of specific features—like those patients who had the lowest hemoglobin levels or had the highest LDH levels—those patients seemed to have a more profound statistically significant survival benefit if they received chemotherapy. As clinicians, we understand that the sickest patients with the most systemic types of progressive cancers will not respond to a second AR-targeted agent.