Current and future standard of care in prostate cancer

Despite several recent advancements in the field of prostate cancer (PC) treatment, there remain distinct gaps in the current standard of care (SoC) and opportunities for improvement, particularly in systemic therapies that could better patients’ lives.

These unmet needs are further complicated by the distinct classifications of PC, defined by hormone sensitivity and metastatic status, which make treatment paths highly individualised. Nevertheless, there is a focused industry effort to improve on the current SoC and to develop new targeted options that not only enhance outcomes, but also improve quality of life (QoL) across all stages of PC.

Several new advancements

In the past few months, several key data releases and approvals have further shaped the PC treatment landscape. One such development is the topline data from Novartis’s Phase 3 PSMAaddition (Pluvicto + ARPi + ADT) in metastsitc hormone sensitive PC (mHSPC), which demonstrated a statistically significant and clinically meaningful rPFS improvement, with a positive trend in OS. This suggests a potential shift away from hormone-only approaches in mHSPC. Building on Pluvicto being the first FDA-approved radioligand therapy (RLT) for PC, this provides Novartis with an even stronger first-mover advantage in early-stage PSMA+ prostate cancer.

Another key data disclosure is from ORIC Pharma’s Phase 1b trial evaluating ORIC-944 (PRC2i) + ARis (apalutamide or darolutamide) in 2L+ mCRPC. This further validates the EZH2 inhibitor class in PC and diversifies potential treatment options for patients in the future

Aside from data disclosures, PC has also seen several recent approvals, including another from Pluvicto in the 2L+ mCRPC setting, which was approved based on PSMAfore and added to NCCN guidelines as a Category 2a Recommendation. This significant approval likely shifts traditional sequencing of NHAs, as Pluvicto’s rPFS advantage and crossover-adjusted OS suggest it offers a more effective option than switching between ARiIs, and overall moves the RLT class into the earlier stages of disease management.

Questions and gaps remain

While biomarker-defined treatment benefits those with specific biomarkers, it leaves significant gaps for patients without them. For instance, Pluvicto demonstrates reduced efficacy in PSMA-low or -negative disease, while Talzenna was not approved for 1L non-HRRm mCRPC based on data from the Phase 3 TALAPRO-2 (approval only in HRRm population). Pairing limited activity in non-mutated tumours and relatively low mutational burden in PC further highlights the limitations of biomarker defined treatment.

Another complicating factor is the inherently “cold” tumour biology of PC, which features poor immune cell infiltration and limited responsiveness to immune activation. This has resulted in low efficacy for immunotherapies that are highly effective in other cancers. Finally, questions remain around treatment sequencing: the current SoC often involves switching NHAs despite limited efficacy, with the alternative being more intensive therapies, sometimes in combination, which raises concerns about overtreatment.

New trials, new solutions

Nevertheless, several promising assets are in the pipeline. Xaluritamig, a bispecific antibody under evaluation in the XALute trial, may offer a breakthrough immunotherapy option for PC, potentially broadening treatment access. Mevrometostat is another promising clinical candidate which targets EZH2i and has the potential to be used broadly as well, not only across biomarker classification, but across all PC subtypes regardless of hormonal sensitivity or pre-treatment. The asset is being evaluated across several trials including MEVPRO-3 (mHSPC), MEVPRO-1 (post-NHA, pre-chemo), and MEVPRO-2 (NHA-naive).

Finally, JANX007 is an example of a PSMA-tumour activated T-cell engager that, being evaluated in ENGAGER-PSMA-01, is positioned to be a potent option for pre-chemo mCPRC patients. These examples represent just a few of the many trials aiming to disrupt the current SoC and improve outcomes.

Looking to the future

With several recent trial readouts and more expected soon, PC remains a hotbed of pharmaceutical innovation. Clinicians and patients alike are waiting to see if RLTs move earlier into the lines of therapy (PSMAaddition: Pluvicto in mHSPC), which further increased competition in the RLT space and brings forward a powerful tool in the treatment of PC. This increased competition, such as via Curium’s ECLIPSE trial (¹⁷⁷Lu-PSMA I&T in post NHA pre chemo) and Telix Pharmaceuticals’ ProstACT trial (TLX591 radioimmuno conjugate- ADC; post NHA, pre/post chemo), will spur innovation and lead to greater achievements in patient care.

The market is also closely observing new immunotherapies that, although historically unsuccessful in PC, may gain traction through novel bi- and tri-specific combinations designed to activate the immune system in a cold tumour environment. Finally, alternative targeted assets are leveraging growing biomarker stratification, enabling more personalised treatment and unlocking new patient groups.

The market also looks out for new immunotherapies which, although that historically have floundered in PC, may succeed moving forward as novel bi- and tri-specific combinations seek to engage the body’s own immune system in a cold tumour environment. Finally, alternatively targeted assets seek to leverage the growing biomarker stratification of the PC market and build on the push to personalise treatment, unlocking new patient groups by leveraging novel targets.

Overall, while the PC market has seen major innovation in recent years, further advancements are on the horizon that will continue to reshape the future standard of care.

About the authors

Mercedes Fleming, PhD, is a senior business analyst at Lifescience Dynamics in London, who earned a doctorate in Cancer Biology from the Institute of Cancer Research in London before transitioning to work in biopharma consulting. She has supported various clients across several indications, including oncology, respiratory, and rare diseases, bringing expertise in competitive intelligence and market research.

Will Torres is a consultant at Lifescience Dynamics. He has over six years of life sciences consulting experience, working across a broad range of therapy areas, including oncology, rare disease, and infectious disease. Torres has managed projects across a broad range of practice areas, such as competitive intelligence, market research, and strategic advisory.

Kasia Koczula is an engagement manager at Lifescience Dynamics, bringing over eight years of consulting experience in the life sciences sector. She holds a PhD in Haematological Oncology and has worked across a broad range of therapy areas, including oncology, cardiovascular diseases, and rare diseases. Koczula specialises in competitive intelligence, market research, and strategic advisory services, supporting clients with evidence-based insights to drive informed decision-making.