What is the clinical benefit of treatment of patients with early breast cancer?

Prof. Ann Partridge (Dana-Farber Cancer Institute, Boston, USA) addressed the relevance of clinical benefit, clinical meaningfulness, and shared decision-making in the treatment of patients with early breast cancer.

Due to improvements in local and systemic treatments, the age-adjusted breast cancer mortality rate has gradually dropped in the last decades: from about 70 per 100,000 women (40-84 years) in the 1970’s to <40 per 100,000 women now. In light of the improved outcomes of the treatment, the definition of clinical benefit of a treatment has also evolved, Partridge said. In the 1970’s, clinical benefit meant that a patient had an objective response to the treatment. In the 1980’s, overall survival, quality of life, and physical functioning became objective parameters to define benefit. Since the 1990’s, the definition is mainly related to surrogate parameters like progression-free survival, overall response rates, durability of responses (in particular in metastatic disease setting), and disease-free survival (in adjuvant setting). Translated to the individual patient, this means that the patient lives longer, feels better (has less symptoms), and/or functions better, Partridge said. To measure all these parameters, several types of assessment are needed: clinician-reported outcomes, observer-reported outcomes, performance outcomes, and – probably most important – patient-reported outcomes.

The concept of clinical benefit has also incorporated the concept of value, Partridge explained. The approval of so many new (and expensive) cancer drugs has shifted focus beyond the statistical improvements of the therapies. Increasingly, the focus is on the clinical value of therapy, both for the individual patient as well as for society. Both ASCO and ESMO recently have developed frameworks to calculate the added clinical value of (new) cancer drugs in a transparent and objective way. ASCO has developed the Net Health Benefit (NHB) scale [1], and ESMO has developed the ESMO Magnitude of Clinical Benefit Scale (MCBS) [2]. Both frameworks factor in outcomes of clinical trials like survival, toxicity, and other symptoms, but also the price of the drug. In the ASCO NHB scale, the added value of the drug is expressed in a number theoretically ranging from -20 to 180 (the higher the score, the greater the added value). In the ESMO MCBS, added clinical value can range from C (lowest added value) to A (highest added value) for potentially curative therapies and from grade 4 (lowest added value) to grade 1 (highest added value) for therapies that are not likely to be curative.

However, therapies that have a high ASCO NHB score or a high ESMO MCBS, e.g. therapies that have clinical benefit, are not necessarily also clinically meaningful, Partridge emphasised. Clinical meaningfulness also depends on individual patient parameters like age, performance status, comorbidities, and personal goals and values. Therefore, thresholds for a therapy being clinically meaningful may be higher or lower for each individual patient (or society). So, in order to define the meaningfulness of an intervention for an individual patient, it is essential to explore the patients’ preferences and personal goals, Partridge said. This is particularly important in situations where there is more than one treatment option (e.g. systemic interventions with different potential therapeutic effects and toxicities, mastectomy vs breast-conserving surgery, or different radiotherapeutic strategies).

Patients’ preferences for the required benefit of an intervention - e.g. the absolute increase of survival or the acceptable treatment toxicity - show a wide range of variation, Partridge illustrated with results from a recent review [3]. In addition, there is a difference between patients and physicians with regard to their definition of a meaningful treatment, and what survival benefit is needed to make adjuvant chemotherapy worthwhile [4]. Physicians, on average, put the bar higher than patients for adjuvant chemotherapy to be worthwhile. However, this study showed that also between physicians’ opinions there is a wide range of variation. Therefore, in every single case it is important to find out what matters to the patient, Partridge concluded. Shared decision-making is a critical factor and, according to the Three-Talk Model of Shared Decision-Making [5], includes talking with the patient, describing the choices, offering support, and asking about their goals. All the options have to be described, including the risks and benefits of every option in the context of what matters to the patient. Finally, the treatment decision is made together with the patient.

1. Schnipper LE, et al. J Clin Oncol 2016; 34: 292502934.
2. Cherny NI, et al. Ann Oncol 2017; 28: 2340-2366.
3. Hamelinck VC, et al. Cancer Treat Rev. 2014; 40:1005-1018.
4. Vaz-Luis I, et al. Cancer 2017; 123: 2821–2828.
5. Elwyn G, et al. J Gen Intern Med. 2012; 27: 1361-1367.

Posted on 21 May 201924 March 2021