1: Earlier abiraterone improves survival for men with advanced prostate cancer: results from STAMPEDE and LATITUDE

The results of two trials presented at ASCO (and published concurrently in the New England Journal of Medicine) show that adding abiraterone plus prednisone to androgen deprivation therapy (ADT) prolongs both progression free and overall survival.

The first of these, an arm of the UK-based STAMPEDE study, was a phase 3, randomised, open label trial. The majority of men were newly diagnosed and they had either metastatic (n=1002; 52%) or non-metastatic (n=915; 48%) disease. Men in the treatment arm (abiraterone + prednisone + ADT) had a 3 year survival of 83% compared to 76% for men receiving ADT alone (HR 0.63; [CI] 0.52-0.76; p<0.001). While there were benefits for men with both metastatic and non-metastatic disease (HR 0.61 and 0.75, respectively), most of the deaths occurred in the metastatic group and further follow up will be required to confirm the effect of abiraterone for men with non-metastatic disease.

The second study, LATITUDE, a double-blind, phase 3 RCT, with a median follow up of 30.4 months, had remarkably similar findings. Median overall survival was significantly longer in the abiraterone treatment group (n=597) compared to placebo control (n=602) (not reached vs. 34.7 months. HR 0.62; [CI] 0.51-0.76; p<0.001), as was radiographic progression-free survival. As expected, in both trials there were more serious adverse effects (grade 3) in the abiraterone arm, most commonly hypertension and hypokalemia, although very few men stopped treatment due to these side effects.

Taken together, these studies show that giving abiraterone early in the treatment pathway can have striking survival benefits for men with advanced prostate cancer. Of note, these trials recruited before docetaxel + ADT became standard of care (following publication of an earlier arm of STAMPEDE) and we do not yet know how the benefits of docetaxel compare to abiraterone. Other questions that need to be answered include whether docetaxel and abiraterone can be administered concurrently or sequentially, and if there is a way to identify men who will respond better to one treatment versus the other. Until we have these answers, the choice of docetaxel or abiraterone will likely come down to a combination of patient and clinician choice, taking into account treatment duration, side-effect profiles, co-morbidities and cost-effectiveness.

2: Monitoring patient reported outcomes improves overall survival for patients with metastatic cancer

One of the most exciting trials to report at ASCO (published concurrently in JAMA) was about the benefits of integrating electronic patient reported outcomes (PRO) into clinical practice. The trial, based at Memorial Sloane Kettering, randomised 766 patients who had metastatic cancer (breast, lung, genitourinary and gynaecological) and were initiating chemotherapy, to a usual care or PRO group. Patients undergoing usual care discussed their symptoms during clinical visits and could contact the office by telephone between visits if they had concerns. Patients in the PRO group received a weekly email prompt to self-report on 12 common symptoms using a web-based system. Severe or worsening symptoms triggered an email alert to an appropriate nurse. Longitudinal symptom reports were provided to the oncologist during clinic visits.

With a median follow up of seven years, patients in the PRO group showed improved median overall survival (31.2mo vs 26.0mo, HR 0.83; [CI] 0.70-0.99; p=0.04) which equates to an 8% survival benefit. Remarkably, this exceeds the survival benefit seen for many of the drugs for advanced cancer that received FDA approval last year. In addition to improved survival, a previous publication also demonstrated that patients in the PRO group had increased improvement in health related quality of life at 6 months, reduced visits to the emergency room and longer duration of chemotherapy use (8.2mo vs 6.3mo). Importantly, these studies also show that patients are willing to self-report (73% reported when prompted) and that clinicians will follow up when alerted (nurses responded to email alerts 77% of the time).

So what accounts for the improved survival? The authors hypothesised that by catching problems at an early stage, patients stay mobile and functional for longer and are able to continue with chemotherapy for longer. What is clear from previous studies is that PRO alone isn’t enough - it has to be integrated with clinical care and responsiveness. Therefore, while this is not a cost-free solution, the success of this trial suggests that regular symptom monitoring should be an important aspect of cancer care going forward.

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3: Curtisen does not improve outcomes for men with castration-resistant prostate cancer

SYNERGY, a phase 3 randomised open-label trial (n=1022), did not show any survival benefit to adding curtisen to docetaxel and prednisone for men with castration-resistant prostate cancer. Curtisen is an inhibitor of the protein Clusterin which is associated with treatment resistance. While addition of curtisen was well-tolerated there was no significant difference in overall survival for men receiving curtisen compared to men in the control group (median survival 23.4mo vs 22.0mo. HR 0.93; [CI] 0.79–1.10; p=0.415).

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