ERLEADA®▼(apalutamide) Significantly Improved Overall Survival and Radiographic Progression-Free Survival in Patients with Metastatic Hormone-Sensitive Prostate Cancer
The Janssen Pharmaceutical Companies of Johnson & Johnson announced today findings from the investigational Phase 3 TITAN study, which showed the addition of ERLEADA® (apalutamide) to androgen deprivation therapy (ADT) compared with placebo plus ADT significantly improved the dual primary endpoints of overall survival (OS) and radiographic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).1 The study included patients with mHSPC regardless of extent of disease or prior docetaxel treatment history.1 Results were presented in an oral session at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract #5006), and simultaneously published online in The New England Journal of Medicine. The data were selected for Best of ASCO 2019 Meetings, which highlight cutting-edge science and reflect leading research in oncology.
Apalutamide plus ADT significantly extended OS compared to placebo plus ADT with a 33 percent reduction in the risk of death (HR=0.67; 95% CI, 0.51-0.89; P=0.0053).1,2 In both study arms, median OS was not reached.1,2 Apalutamide plus ADT also significantly improved rPFS compared to placebo plus ADT with a 52 percent reduction in risk of radiographic progression or death compared to placebo plus ADT (HR=0.48; 95% CI, 0.39-0.60; P<0.0001).1,2 The median rPFS was 22.1 months for placebo plus ADT and not reached for apalutamide plus ADT.1,2 The two-year OS rates, after a median follow up of 22.7 months, were 82 percent for apalutamide plus ADT compared to 74 percent for placebo plus ADT.1,2
These data formed the basis of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking approval of a new indication for apalutamide for the treatment of patients with mHSPC, which is currently under review through the Real-Time Oncology Review (RTOR) programme.3
“The data presented today mark a major scientific evidence milestone in the management of patients with mHSPC,” said Prof. Dr. med. Axel S. Merseburger, Chairman of the Department of Urology, Campus Lübeck, University Hospital Schleswig-Holstein. “The TITAN data has shown that apalutamide could significantly benefit patients by delaying disease progression and critically, prolong overall survival in a disease where median overall survival is less than five years. It is clinically relevant to see that this trial has demonstrated that apalutamide has the potential to benefit all types of patients with mHSPC and I am incredibly proud to be a part of this study.”
In addition to meeting the primary dual endpoints of OS and rPFS, the secondary endpoint of prolonged time to cytotoxic chemotherapy in patients treated with apalutamide plus ADT was also met, with a 61 percent risk reduction compared with placebo plus ADT (HR=0.39; 95% CI, 0.27-0.56; P<0.0001).1,2 In exploratory endpoints, median time to PSA progression was more favourable following apalutamide plus ADT, compared with placebo plus ADT, and PSA reached undetectable levels in 68 percent of patients in the apalutamide plus ADT arm and 29 percent in patients in the placebo plus ADT arm.1,2 Additionally, apalutamide plus ADT, compared with placebo plus ADT, achieved a 34 percent risk reduction in median time to second progression-free survival (PFS2), defined as time from randomisation to either disease progression on first subsequent anticancer therapy or death, whichever occurred first (HR= 0.66; 95% CI, 0.50-0.87).1,2 The median PFS2 was not reached for both study arms. Although time to pain progression was tested, it did not reach statistical significance.1,2 Due to a hierarchical statistical design, no formal testing for further secondary endpoints, including median time to chronic opioid use and median time to skeletal-related events, were conducted at this time.1,2
Adverse events (AEs) were generally consistent with the known apalutamide safety profile. The incidence of Grade 3/4 AEs for apalutamide plus ADT, versus placebo plus ADT were similar (42 percent vs 41 percent).1,2 The most common Grade 3 AEs for apalutamide plus ADT versus placebo plus ADT were hypertension (8.4 percent vs. 9.1 percent) and skin rash (6.3 percent vs. 0.6 percent).1,2 Additional reported Grade 3 AEs for apalutamide plus ADT versus placebo plus ADT were back pain (2.3 percent vs. 2.7 percent), blood alkaline phosphatase increased (0.4 percent vs. 2.5 percent) and anemia (1.7 percent vs. 3.2 percent).1,2 Treatment discontinuation due to AEs was 8 percent in the apalutamide arm compared to 5 percent in the placebo arm.1,2 Rash of any grade was more common among patients treated with apalutamide plus ADT, versus placebo plus ADT (27 percent vs 9 percent, respectively).1,2
“This is the first presentation of the investigational TITAN data. We are encouraged that apalutamide significantly improved overall survival and in a relevant magnitude, underscoring that the efficacy of treatment with ADT alone could offer to patients with mHSPC was, actually, inferior to that provided by apalutamide,” said Dr. Joaquín Casariego, Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen Cilag SA. “Our mission as physicians is to treat the patient with the right treatment at the right time. We will continue in our endeavors to improve outcomes for patients, through engagement with the investigators’ community in robust clinical research studies, such as TITAN, that could help answer the most relevant health questions for patients suffering from cancer, their HCPs and all stakeholders involved in the fight against this disease.”
Apalutamide plus ADT significantly extended OS compared to placebo plus ADT with a 33 percent reduction in the risk of death (HR=0.67; 95% CI, 0.51-0.89; P=0.0053).1,2 In both study arms, median OS was not reached.1,2 Apalutamide plus ADT also significantly improved rPFS compared to placebo plus ADT with a 52 percent reduction in risk of radiographic progression or death compared to placebo plus ADT (HR=0.48; 95% CI, 0.39-0.60; P<0.0001).1,2 The median rPFS was 22.1 months for placebo plus ADT and not reached for apalutamide plus ADT.1,2 The two-year OS rates, after a median follow up of 22.7 months, were 82 percent for apalutamide plus ADT compared to 74 percent for placebo plus ADT.1,2
These data formed the basis of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking approval of a new indication for apalutamide for the treatment of patients with mHSPC, which is currently under review through the Real-Time Oncology Review (RTOR) programme.3
“The data presented today mark a major scientific evidence milestone in the management of patients with mHSPC,” said Prof. Dr. med. Axel S. Merseburger, Chairman of the Department of Urology, Campus Lübeck, University Hospital Schleswig-Holstein. “The TITAN data has shown that apalutamide could significantly benefit patients by delaying disease progression and critically, prolong overall survival in a disease where median overall survival is less than five years. It is clinically relevant to see that this trial has demonstrated that apalutamide has the potential to benefit all types of patients with mHSPC and I am incredibly proud to be a part of this study.”
In addition to meeting the primary dual endpoints of OS and rPFS, the secondary endpoint of prolonged time to cytotoxic chemotherapy in patients treated with apalutamide plus ADT was also met, with a 61 percent risk reduction compared with placebo plus ADT (HR=0.39; 95% CI, 0.27-0.56; P<0.0001).1,2 In exploratory endpoints, median time to PSA progression was more favourable following apalutamide plus ADT, compared with placebo plus ADT, and PSA reached undetectable levels in 68 percent of patients in the apalutamide plus ADT arm and 29 percent in patients in the placebo plus ADT arm.1,2 Additionally, apalutamide plus ADT, compared with placebo plus ADT, achieved a 34 percent risk reduction in median time to second progression-free survival (PFS2), defined as time from randomisation to either disease progression on first subsequent anticancer therapy or death, whichever occurred first (HR= 0.66; 95% CI, 0.50-0.87).1,2 The median PFS2 was not reached for both study arms. Although time to pain progression was tested, it did not reach statistical significance.1,2 Due to a hierarchical statistical design, no formal testing for further secondary endpoints, including median time to chronic opioid use and median time to skeletal-related events, were conducted at this time.1,2
Adverse events (AEs) were generally consistent with the known apalutamide safety profile. The incidence of Grade 3/4 AEs for apalutamide plus ADT, versus placebo plus ADT were similar (42 percent vs 41 percent).1,2 The most common Grade 3 AEs for apalutamide plus ADT versus placebo plus ADT were hypertension (8.4 percent vs. 9.1 percent) and skin rash (6.3 percent vs. 0.6 percent).1,2 Additional reported Grade 3 AEs for apalutamide plus ADT versus placebo plus ADT were back pain (2.3 percent vs. 2.7 percent), blood alkaline phosphatase increased (0.4 percent vs. 2.5 percent) and anemia (1.7 percent vs. 3.2 percent).1,2 Treatment discontinuation due to AEs was 8 percent in the apalutamide arm compared to 5 percent in the placebo arm.1,2 Rash of any grade was more common among patients treated with apalutamide plus ADT, versus placebo plus ADT (27 percent vs 9 percent, respectively).1,2
“This is the first presentation of the investigational TITAN data. We are encouraged that apalutamide significantly improved overall survival and in a relevant magnitude, underscoring that the efficacy of treatment with ADT alone could offer to patients with mHSPC was, actually, inferior to that provided by apalutamide,” said Dr. Joaquín Casariego, Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen Cilag SA. “Our mission as physicians is to treat the patient with the right treatment at the right time. We will continue in our endeavors to improve outcomes for patients, through engagement with the investigators’ community in robust clinical research studies, such as TITAN, that could help answer the most relevant health questions for patients suffering from cancer, their HCPs and all stakeholders involved in the fight against this disease.”
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