1. Relevant Endpoints for Advanced
Breast Cancer Patients
Patricia A. Ganz, M.D.
UCLA Schools of Medicine & Public Health
Jonsson Comprehensive Cancer Center
ABC-1 Conference
November 3-5, 2011

2. The many faces of ABC is a challenge…….
Disease & patients are
heterogeneous, with
different needs and goals
• Newly diagnosed with
metastatic disease—HER
2 + vs. negative
• Endocrine
responsive, slowly
progressing
• Rapidly progressing triple
negative
• Young vs. older
• Soft tissue/bone vs.

3. ‘Treatment for metastatic breast cancer is
lifelong and focuses on control and quality of
life vs. curative intent. ("Treatable but
unbeatable.“)’
From 13 facts everyone should know about
metastatic breast cancer. www.mbcn.org

4. • What happens when breast cancer recurs?
– Significant decline in physical functioning, social
functioning and health perceptions
– Increased intrusive and avoidant thoughts

5. Most Prevalent Symptoms

6. Relationship between Symptoms and
QOL
Symptoms are more sensitive to change over time than QOL.
Sarenmalm, et al. 2008

7. Living with advanced
breast cancer and the
Sword of Damocles……
When disease or dis-ease threatens us or
our loved ones, it's the forethought of
loss, of pain, of grief that flips on the
anxiety switch.
When our friends and colleagues are
losing their jobs, when we see media
coverage of layoffs, we feel badly for
others but we also see that sword over
our own heads and imagine it coming
down on us.
http://middle-aged-diva.blogspot.com/2011/03/anticipation-worry-
cut-from-same-cloth.html

8. Challenges of Metastatic Breast Cancer
Maintenance of
Symptom Control
Independence
Cancer as a
chronic
disease
Management of
Social Support &
Anxiety &
Social Isolation
Depression

9. What are the goals of therapy in ABC?
• Symptom control
• Prolonged remission or stable disease
• Prevention of disease-related morbidity,
e.g. pathologic fracture, hypercalcemia
• Maintenance of physical functioning and
ability to care for self
• Reduction in psychological morbidity that is
affected by disease burden and health status

10. What are the burdens of therapy?
• Acute and chronic
toxicities, e.g., neuropathy, fatigue, hair
loss, mucositis
• Time spent in treatment—complex vs. simple
regimens, oral vs. intravenous
• Financial/economic loss—out of pocket, time
lost from work, family caregiving time
• LIVING WITH ONGOING DISEASE
AND SYMPTOMS

11. Balancing the goals and burdens…
Treatment
Toxicity
Treatment
Benefit

12. Focus on Patient Reported Outcomes
(PROs) in Advanced Breast Cancer
• Challenge to collect these data in ABC when
disease is rapidly progressing
– Missing data, inadequate sample size and power (see
Goodwin et al. JNCI, 2003)
• Quality of Life scales are not usually
discriminating and symptoms have been less
frequently measured (see Lemieux et al.
JNCI, 2011)
• Assessment of symptoms with PROs, especially
targeting pain, fatigue, physical limitations may
be necessary

13. Relevant Endpoints
• Progression free-survival???
– Need concomitant PROs that support improved
symptoms, function, and no serious AEs
• Stable disease???
– Need concomitant PROs to support stable or
improved symptoms, function, and no serious AEs
• Symptom benefit/improvement/control
– Use of composite endpoints that demonstrate
improvement in serious symptoms, e.g.
pain, fatigue, without requirement of measurable
response or prolongation of life

14. Conclusions
• There are several potential endpoints to
consider in advanced breast cancer
• Prioritization should reflect the particular
disease setting and patient population
• Incorporation of PROs that focus on symptom
control, improved physical function, and
prevention of disability, may enhance the
value of more traditional disease-
response/survival outcomes

15. Recommendations
• Phase III RCTs should measure PROs of symptoms
and functioning to assess needs of ABC
patients, and to measure impact of treatment on
these outcomes
• Drug approval and sequencing of therapies
should include PRO symptom outcomes as a
major endpoint
• Patients with ABC should be classified by disease
characteristics AND symptoms to better match
treatments to relevant outcomes

16. ‘Treatment for metastatic breast cancer is
lifelong and focuses on control and quality of
life vs. curative intent. ("Treatable but
unbeatable.“)’
From 13 facts everyone should know about
metastatic breast cancer. www.mbcn.org