By Suneel Mundle, Ph.D., Sr. Global Medical Affairs Lead
Tremendous strides in the development and delivery of prostate cancer treatments have been made by researchers around the world — and new advances are on the horizon. As the second-most common cancer in men and the fourth-leading cause of cancer death in men worldwide, prostate cancer accounts for approximately 1.4 million cancer diagnoses and 375,000 deaths annually.1 A nuanced, multi-pronged approach is needed to deliver more effective therapies to patients with prostate cancer that aim to not only increase survival rates, but also maintain quality of life.
The prostate cancer treatment landscape forever changed with the discovery that androgens are a strong driver of the disease — meaning that male hormones such as testosterone stimulate prostate cancer cell growth. Lowering a patient’s androgen levels using hormonal therapies has proven effective in slowing disease progression and increasing overall survival in many patients.
As more patients are living longer with prostate cancer, Janssen is moving beyond conventional measures and indicators, such as long-term survival, patient-reported outcomes (PROs), radiographic progression-free survival and metastasis free survival. One such early indicator used in clinical research is serum prostate-specific antigen (PSA). Janssen is focused on endpoints that matter to patients and their physicians, particularly early indicators of treatment response.
PSA is a protein produced by both normal and malignant cells of the prostate gland that is typically elevated in patients with prostate cancer. The relationship between elevated PSA levels and prostate cancer was first reported in the 1980s. Since then, PSA tests have been widely used in routine prostate cancer screening.
For patients already diagnosed with prostate cancer, ongoing PSA monitoring is an important quantitative measure of treatment response. Many patients anxiously await their latest PSA results, and some even view decreases in PSA as a more important treatment goal than improvement in symptoms.2 On the other hand, patients with sustained, elevated PSA levels have been reported to have higher rates of anxiety and depression. One study even demonstrated that patients’ psychological distress increased as their PSA levels rose, and decreased when their PSA levels fell back within the normal range.3
Post-hoc analyses from Janssen’s Phase 3 clinical trials in prostate cancer have shown that rapid and deep PSA decreases of ≥90 percent from baseline within three months of treatment initiation correlated with longer overall survival and maintained quality of life.4,5 Janssen’s ongoing evaluation of PSA levels during treatment and how they correlate with clinical outcomes as well as PROs may offer much-needed insights to patients and physicians as they navigate treatment decisions and seek to regain peace of mind.
PSA monitoring, however, is just one piece of an individualized treatment approach. Prostate cancer is a complex disease that may be driven by several specific genetic mutations in cancer cells, and the type of mutation can affect how a patient responds to treatment. Patients can be diagnosed at different disease stages (e.g., metastatic and non-metastatic), and tumors can be either hormone-resistant or hormone-sensitive. Recognizing these complexities, Janssen is advancing prostate cancer research and therapeutic options with each patient’s needs at the forefront. Janssen’s robust portfolio and pipeline of therapeutics span multiple modalities and stages of disease as researchers evaluate additional indications for existing therapies and develop new therapeutics with novel mechanisms of action (MOAs).
Diagnosing and treating prostate cancer early — with the most precise and aggressive intervention available — may provide patients the best chance at survival. While nearly 75 percent of U.S. patients with prostate cancer are diagnosed at the localized stage, the percentage of patients diagnosed with metastatic disease doubled from four percent in 2003 to eight percent in 2017. Although survival rates have improved for all prostate cancer stages, fewer than a third of patients with advanced disease are alive five years after diagnosis.
It is clear that the current standard of care is not enough for many patients with prostate cancer. Janssen believes these patients could derive long-term benefits from earlier intervention with more therapeutic interventions and/or targeted approaches. Multi-modality approaches of androgen-deprivation therapy with a combination of agents, including newer hormonal therapies, has been demonstrated to increase overall survival time in patients with metastatic prostate cancer.
One MOA that Janssen is investigating for targeted therapy is poly ADP ribose polymerase (PARP) inhibition. PARP inhibitors have shown efficacy in patients with metastatic disease who have homologous recombination repair (HRR) gene alterations, specifically mutations in the BRCA1 and BRCA2 genes. Patients whose tumors bear these mutations typically have a worse prognosis and a poorer response to standard of care than patients without HRR mutations.6
Through prospectively designed clinical trials, Janssen aims to not only unlock the potential of PARP inhibition and other agents with novel MOAs, but also to better identify patients who will derive the most benefit from each of these therapies. Insights from clinical research will provide clear guidance to physicians, enabling them to make the best treatment recommendations for their patients.
As Janssen looks to the future of prostate cancer treatment, one thing is clear: the days of a one-size-fits-all approach are long gone. To meet the challenges of this complex disease and deliver better outcomes for all patients, individual therapeutic needs must be addressed. Janssen is doing this by evolving the understanding of the biological factors that impact the disease, advancing from new and innovative therapeutics, and keeping PROs and other indicators of quality of life front and center.
1 IARC. Cancer Today – Estimated number of new cases in 2020, worldwide, both sexes, all ages. Available at https://gco.iarc.fr/today/home. Accessed March 2022.
2 Lofters A, Juffs HG, Pond GR, Tannock IF. "PSA-itis": knowledge of serum prostate specific antigen and other causes of anxiety in men with metaststic prostate cancer. J Urol. 2002;168(6):2516-2520.
3 Kobayashi M, Nukui A, Kamai T. Psychological impact of serial prostate-specific antigen tests in Japanese men waiting for prostate biopsy. Int J Clin Oncol. 2017;22(1):174-180.
4 Small et al. Association Between Patient-Reported Outcomes (PROs) and Changes in Prostate-Specific Antigen (PSA) in Patients (pts) with Advanced Prostate Cancer Treated with Apalutamide (APA) in the SPARTAN and TITAN Studies. ASCO GU 2022.
5 Chi et al. Prostate-Specific Antigen Kinetics in Patients With Advanced Prostate Cancer Treated With Apalutamide: Results From the TITAN and SPARTAN Studies. AUA 2021.
6 Dhawan M, et al. DNA Repair Deficiency Is Common in Advanced Prostate Cancer: New Therapeutic Opportunities. Oncologist. 2016;21(8):940-945.