Despite being the subject of immense research efforts, breast cancer remains the second most common cause of death for cisgender women in the US. (1) The majority of these fatalities are due to the development of metastatic disease (cancer that has spread to another part of the body). (2,3) While largely affecting cisgender women, breast cancer affects people of all sexes and genders. (4,5) 

Although metastatic breast cancer is incurable and associated with a high symptom burden, (6-8), it can be treated (9) – and the need for optimising metastatic breast cancer care is growing as more and more people live longer with metastatic breast cancer due to advances in therapies. (10) How treatments are best evaluated varies between different types and stages of cancer, and this particularly applies in the case of metastatic disease. In 2020, a multistakeholder steering committee sponsored by Eli Lilly and Company found that some issues relevant to people living with metastatic breast cancer, including patients’ priorities, burden of disease, and metastatic breast cancer-specific quality of life, are “not consistently considered in the current benefit assessment process of new treatments”. (9) While it is always important (and inherent to patient-centred care) to assess treatments in line with the priorities of the people who need them, it is particularly crucial that the needs, wants, and quality of life (QoL) of patients with metastatic breast cancer are considered, given the life-limiting nature of the disease and the unavailability of curative treatment. (11) 

Health outcomes are defined as “events occurring as a result of an intervention”, (12) and include examples such as changes in pain or blood pressure. (13) Outcome information is often gathered (‘reported on’) by people working on clinical trials, but data can also be collected in the form of patient-reported outcomes (PROs). 

Collecting PRO data can help researchers, regulators, clinicians, and more to understand how treatments affect patients more comprehensively than solely within traditional dimensions (drug safety and efficacy). Furthermore, if PROMs are chosen/designed in collaboration with patients, drug developers can ensure that treatments are assessed in line with patients’ real priorities. The value of conducting these assessments in clinical trials may be boosted further by the use of disease-specific PROs, (16,17) or even disease stage-specific PROs, which enhance the relevance of the outcomes included – for example, hypothetically, the ability to work may be considered a much less relevant outcome for people living with metastatic breast cancer than those with earlier-stage disease.  

Despite the rich insights PRO data can reveal, many trials do not include PROMs in study design – meaning stakeholders from researchers to patients often lack access to valuable information about novel treatments. Where PROMs are included, regulators often consider the methodology unsound, exacerbating this information gap. Proactive alignment between industry and regulatory bodies is urgently required to ensure PRO data are not collected in vain. (19) 

“It is key that…the information collected [through metastatic breast cancer PROMs] is used in a specified analysis, ideally as a secondary endpoint, not simply an exploratory one.”

– Siedman et al. (20)

Regulatory and Health Technology Assessment bodies

Composed correctly, PRO data can help address some common challenges facing organisations that assess the value of new metastatic breast cancer treatments – whether they be regulators, who decide if treatment is safe and effective, or Health Technology Assessment (HTA) agencies, who assess the relative value of treatment within the wider context of ethics, economics, and clinical considerations. (21) PRO data can strengthen drug companies’ submissions to both kinds of organisation, as well inform treatment decisions by clinicians and patients. 

For regulators, PRO data can demonstrate efficacy beyond the usual clinical endpoints, which is particularly valuable when a treatment’s efficacy (as defined via traditional measures) is not superior to that of existing products, but that treatment offers patient-relevant benefit that can only be captured via other means (i.e., PRO data collection). 

PRO data provide vital context

For both regulators and HTA bodies, PRO data can help alleviate a common challenge to decision-making regarding new cancer treatments – lack of preferred survival data. (9,22) For these organisations, overall survival (OS) data are preferred over progression-free survival (PFS) data for assessing treatment value. (9,22,25,26) One reason for this is that an improvement in PFS does not consistently translate into an improvement in OS, (22,27-32) and therefore does not necessarily answer the ultimate question of whether a treatment may impact life expectancy.  

Given the limitations of PFS data, PRO data can be a particularly useful addition to a treatment’s evidence base when OS data are not available. Indeed, due to the urgency of making novel cancer treatments available, it is common for insufficient time to have passed to facilitate the collection of satisfactorily mature OS data when treatment efficacy or relative value are being assessed. (26) In situations like this, PRO data (which can be collected sooner than those pertaining to OS) can contextualise efficacy with tolerability from patients’ perspectives – a particularly key source of information given that compared to patient reports, clinician-assessed toxicity gradings may miss up to half of adverse events. (34) This helps to support the meaningful evaluation of treatments in lieu of OS data and in conjunction with PFS data. (11,20)  

QoL data are another source of important context for efficacy data, as QoL is one of the endpoints most valued by people living with metastatic breast cancer. (35) While physicians can collect QoL data from patients, it’s more appropriate to approach QoL as a PRO, as for patients with metastatic breast cancer, substantial variability has been demonstrated between QoL ratings by physicians and those by patients. (36) 

“Assessments of the overall benefit of metastatic breast cancer treatments are more valuable when, in addition to factoring in the survival benefit, they are informed by patients’ needs and priorities with respect to health-related quality of life and ability to participate in daily life activities.”

– Cardoso et al. (9)

Clinicians and patients

If OS data are available, given that oncologists must weigh up treatment impact on quality of life as well as survival duration, PRO data can be the key link between proving an improvement to OS is not only statistically significant, but also clinically meaningful. (37) This provides vital, relevant detail to help empower clinicians to differentiate between treatment options and select that which is most appropriate for each individual patient. The same also applies more generally; when efficacy across multiple treatment options is comparable but drug toxicity profiles differ, PRO data can help oncologists to interpret the impact of different treatments on quality of life, symptom burden, and more, and thus make better-informed choices as to which treatment is most suitable for each patient. (38) 

Similarly, PRO data are valued by patients, as these results can enhance communication between patients and their clinicians about treatment options and thus empower patients to partake in shared decision-making regarding their care. (39) What’s more, as PRO data can support regulatory and HTA decisions, PRO data have the potential to facilitate a major priority for many patients – having choices as to which treatment(s) they wish to receive. 

“PROs can provide valuable information about trade-offs between benefits and adverse events of breast cancer treatments and reduce the burdens from breast cancer symptoms and adverse events of breast cancer treatments simultaneously.”

– Rivera et al. (19)

Where are we now?

Room for improvement: As of 2019, it was apparent that despite the FDA having released guidance on the implementation of PROs in clinical trials ten years prior, there had been minimal change in the use of PROs as endpoints in metastatic breast cancer studies. (40) What’s more, despite the emergence of recommendations for PROMs (e.g., HRQoL questionnaires) to be disease-specific, as of 2021, it remained common in metastatic breast cancer research for more generalised measures to be used instead. (11) 

The bright side: the European Organisation for Research and Treatment of Cancer, the European School of Oncology (ESO), and the ABC Global Alliance are currently collaborating to develop an up-to-date, standardised, and patient voice-informed PROM focusing on health-related QoL in metastatic breast cancer. (9,11) This will hopefully result in greater implementation of high-quality PROs in metastatic breast cancer trials and treatment decisions – and ultimately, more patient-centred care for every person living with metastatic breast cancer. 

• Prime Patient is a specialist consultancy delivering strategic patient engagement solutions to achieve a triple win for patients, Pharma, and society. For more information, get in touch via PatientEngagement@primeglobalpeople.com.

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