Apalutamide in combination with ADT prolonged median overall survival by 14 months and decreased the risk of death by 22%.
Median overall survival was significantly longer, with 73.9 months for patients receiving treatment with Apalutamide in combination with ADT compared to 59.9 months with patients receiving placebo in combination with ADT [ hazard ratio, HR=0.78; p=0.0161 ( to reach statistical significance, a p-value of p less than 0.046 needed to be observed ) ].
After the study met its primary endpoint of metastasis-free survival ( MFS ), the SPARTAN study was unblinded and patients on placebo were allowed to crossover to Apalutamide.
The OS results were achieved despite a crossover of 76 randomized placebo patients ( 19% ) to Apalutamide treatment.
After adjusting for the crossover of patients in the placebo arm, the treatment effect of Apalutamide plus ADT exceeded median OS compared to placebo plus ADT with a difference of 21 months between the two arms ( 73.9 months vs 52.8 months, respectively, HR=0.69, p=0.0002 ).
Additionally, treatment with Apalutamide in combination with ADT significantly delayed patients' time to cytotoxic chemotherapy compared to placebo in combination with ADT ( HR=0.63; p=0.0002 ).
Together with data from the primary analysis, the SPARTAN study has met all primary, secondary and exploratory endpoints.
The primary endpoint of the study was MFS; the secondary endpoints were time to metastasis, progression-free survival ( PFS ), time to symptomatic progression, OS and time to initiation of cytotoxic chemotherapy; and the exploratory endpoints were second progression-free survival ( PFS2 ), prostate specific antigen ( PSA ) responses and risk of PSA progression.
Median treatment duration was nearly three times longer for patients treated with Apalutamide plus ADT ( 33 months ) compared with the those treated with placebo plus ADT ( 12 months ).
Grade 3/4 treatment-emergent adverse events of special interest were rash ( 5.2% ), fractures ( 4.9% ), falls ( 2.7% ), ischemic heart disease ( 2.6% ), hypothyroidism ( 0% ) and seizures ( 0% ).
Safety and tolerability of Apalutamide is consistent and as reported previously.
Non-metastatic castration-resistant prostate cancer refers to a disease stage in which the cancer no longer responds to treatments that lower testosterone but has not yet been discovered in other parts of the body using a total body bone scan and/or CT/MRI scan.
Features include: lack of detectable metastatic disease using conventional radiographic imaging and rapidly rising PSA while on ADT with serum testosterone level below 50 ng/dL.
Ninety percent of patients with nmCRPC will eventually develop metastases, which can lead to pain, fractures and other symptoms.
The relative five-year survival rate for patients diagnosed with a distant-stage prostate cancer is 31%. It is critical to delay the development of metastasis in patients with nmCRPC.
Source: Janssen, 2020