Insider Interview: Paving paths in prostate cancer

Joaquin Casariego Garcia Luben, Medical Affairs Director Europe, Middle East & Africa, Prostate Cancer for Johnson & Johnson (pictured) discusses Janssen’s vision in Oncology and how the company is building on its heritage in prostate cancer to deliver transformational outcomes for patient.

What is Janssen’s vision in oncology?

We are striving to make cancer a more manageable – even curable – condition, and at the very least provide meaningful chronification. Despite the incredible work of the oncology community, cancer remains the second leading cause of premature death in Europe, causing one in four deaths in Europe, with around 1.9 million deaths from cancer in 2018.

At Janssen, we understand that every patient with cancer faces a unique journey and so we want to treat them in a unique way, accounting for individual differences in people’s genes, environments and lifestyles. Through precision medicine, we are abandoning a simplistic ‘one-size-fits-all’ approach to cancer research and development to find the right treatment for the right patient at the right time. We are focusing our efforts on discovering best-in-class, innovative medicines for cancer types where patient needs are greatest and pursuing cancer sub-types in which we can achieve the highest impact. This approach will allow us to truly transform patients’ lives today and move towards a cure tomorrow.

Janssen has a heritage in prostate cancer. What key challenges does the disease present compared to other forms of cancer?

Prostate cancer is the most common cancer in men in the European Union (EU), representing 25% of all new male cancer cases. Two key challenges that we face in the management of prostate cancer are:

i) Initial symptoms do not often present until later-stage disease, when the cancer has spread from the prostate to other parts of the body. Metastatic disease is a major cause of complications and death among those with prostate cancer.

ii) Some patients will eventually become resistant to treatments; as the cancer progresses, there is an increase in tumour heterogeneity that often means patients can become less responsive to treatments.

The course of prostate cancer is determined by the presence or risk of developing metastatic disease and therefore delaying metastases is critical to improving patient outcomes and prolonging survival. It is crucial that effective medicines are made available to patients earlier in the course of their disease, and personalised medicine is harnessed to diagnose and intercept cancer at its earliest stages and to reduce drug resistance.  

How have survival rates for prostate cancer patients changed over the last decade?

Prostate cancer survival rates have dramatically increased over the last few decades, with mortality rates in the EU declining by approximately 20% between the late 1980s and 2010. These positive shifts can be attributed to improved early detection of tumours, improvements in surgery and radiotherapy as primary curative treatments, the availability of novel innovative medicines, initiation of treatment at earlier stages and the development of strong clinical guidelines.

How can we improve even further on these rates? What obstacles still need to be overcome to make this happen?

When we look at the relative five-year survival rate by disease stage, metastatic prostate cancer patients only have a 30% survival rate. This means that we need to bring new treatments to patients at earlier stages of their disease before the cancer has spread to other parts of the body and when patients are more likely to benefit.    

Prostate cancer is subject to a personalised medicine approach, both in the research and clinical settings. There remains a need for even more accurate risk stratification towards the identification of cancer subpopulations with different prognoses, and on finding predictive factors for responses to the different therapies. The biomarker research field, which includes clinical, genomic, metabolomic, psychological and behavioural factors, is rapidly expanding in prostate cancer. Artificial intelligence is becoming a critical tool for integrating all this information in an accurate and efficient way. Similarly, next-generation imaging techniques are opening a new world for decision making.

Importantly, through this approach we need to characterise the molecular and genetic mechanisms of tumour cells that lead to drug resistance and create new tests to detect the presence of abnormalities in the androgen receptor, which plays a crucial role in the development and maintenance of the prostate. This will allow us to unlock new ways to diagnose and stop the cancer before it can take hold in the body – a process known as cancer interception.

How does the EU approval of Erleada (apalutamide) earlier this year push the treatment of prostate cancer and achieve better outcomes for patients?

At Janssen, we pioneered a novel development strategy in how medicines are evaluated and approved, bringing effective treatments into the hands of patients sooner, before their disease progresses. Apalutamide, a next-generation oral androgen receptor inhibitor, became the first medicine to be approved by the FDA, and subsequently the European Commission, for the treatment of patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) using metastasis-free survival (MFS) as the primary end point and a potential surrogate for overall survival (OS). It was also first made available for patients with early-stage rather than late-stage disease, marking a step change in the prostate cancer treatment landscape.

Apalutamide has been shown to decrease the risk of distant metastasis or death by 72% and improve median MFS by more than two years, compared to placebo. It is important that the spread of prostate cancer is prevented as median survival for patients with metastatic castration-sensitive prostate cancer (mCRPC) is usually only three years.

What about Janssen’s other projects in prostate cancer? What research trends are driving drug discovery and development?

At Janssen, we are committed to bringing medicines to patients at the earliest stages of their disease where there is potential for cure or at least a meaningful chronification. Following approvals for apalutamide in high-risk nmCRPC, we are now investigating the medicine:

• In the Phase 3 ATLAS study, for the treatment of high-risk localised or locally advanced prostate cancer in patients receiving radiotherapy, using MFS as a primary endpoint
• In the Phase 3 PROTEUS study for the treatment of high-risk localised or locally advanced prostate cancer in patients receiving androgen deprivation therapy (ADT) before and after radical prostatectomy. The co-primary endpoints in this trial are MFS and pathological complete response (pCR)

However, our research programme does not forget the ongoing needs of patients living with metastatic disease, where survival rates are low compared to early-stage disease.  The ongoing Phase 3 TITAN study, which was unblinded earlier this year, is evaluating apalutamide plus ADT versus placebo plus ADT in men with metastatic castration-sensitive prostate cancer (mCSPC). Through TITAN, we hope to provide apalutamide to patients suffering from mCSPC so that they can live longer and with a good quality of life.

Beyond these Phase 3 studies, the Phase 2 GALAHAD study is exploring niraparib, an orally-administered poly (ADP-ribose) polymerase (PARP) inhibitor for third-line treatment of adult men with mCRPC with DNA-repair pathway defects. Preliminary results suggest that PARP inhibition with niraparib may play an important role in the treatment of men with mCRPC who have mutations in DNA-repair genes. This means prospective biomarker testing could enable healthcare professionals to personalise therapy for patients with mCRPC in the future, leading to better outcomes.

Given what we’ve discussed, what are your predictions, or perhaps your hopes, for the space over the next few years?

At Janssen, patients and their families are at the heart of everything we do. Our efforts will continue in prostate cancer so long as there are still people who need new treatment options. For them, we dedicate ourselves to developing transformational treatment solutions that we hope will continue to not only prolong survival but also improve lives.

We are making great progress on our journey towards changing what a prostate cancer diagnosis means, as we work towards our vision of making prostate cancer a potentially curable disease.