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Dr Reshma Mahtani discusses key breast
cancer trials at ASCO 2016
Reshma L. Mahtani DO, is Assistant
Professor of Clinical Medicine at the
Sylvester Comprehensive Cancer
Center at the University of Miami.
Extending endocrine therapy
The MA.17R study
1
looked at patients who had received 5 years of an aromatase inhibitor,
either up front for 5 years or after 2 to 3 years of tamoxifen. These patients were randomised
to an additional 5 years of an aromatase inhibitor (letrozole) versus placebo. At 5 years of
follow up, 95% of women receiving letrozole and 91% of those receiving placebo were breast
cancer-free. The 34% lower risk of recurrence associated with continuation of letrozole is
clinically meaningful. However, the take-away point is that over 90% of patients in both arms
were disease-free, which highlights the fact that patients this far out from a breast cancer
diagnosis are doing quite well. These small incremental gains that we’re making really have
to be balanced against the side effects and toxicities of the therapy. Patient overall quality of
life was comparable between the two groups; however, this analysis is, of course, selected
for those patients who were able to tolerate the first 5 years of therapy, and doesn’t take into
account all those patients who came off therapy earlier on for quality-of-life issues.
Efficacy of adding a CDK4/6 inhibitor to endocrine therapy
For patients with metastatic ER-positive/HER2-negative breast cancer, the PALOMA-2 trial
2
confirmed the results of PALOMA-1 by demonstrating that the addition of the CDK4/6 inhibitor
palbociclib to letrozole in the first-line setting was associated with a significant improvement in
progression-free survival (PFS).
The important finding was a 10-month difference in PFS. It didn’t quite meet the doubling
in PFS of 10 to 20 months that we saw in PALOMA-1; however, 14.5 to 25 months is still
quite remarkable and is, of course, clinically meaningful. Aside from the efficacy data, the
psychological impact of being able to tell a patient that she is doing well on her anticancer
therapy should not be minimised. Finally, there
were no new safety signals, the drug is very
well-tolerated, and the results confirm the
efficacy noted in the first-line setting in the
earlier phase 2 study.
A biomarker that’s prognostic, but
also predictive of endocrine therapy
benefit
Endocrine therapy is not without toxicities,
and, if we look across the board at all of the
extended endocrine studies, we’ll notice that
the absolute magnitude of benefit is about 3%
to 5% with the addition of extended endocrine
therapy. This really highlights the need to
have a biomarker to identify which patients
will benefit. Not only do we need a biomarker
that’s prognostic, but one that is also predictive
of endocrine therapy benefit. There are several
diagnostic assays that are looking at this. In my
opinion, the Breast Cancer Index is the one
that has gone the farthest in having data in both
the prognostic and predictive areas.
Assessing the right assay for
molecular profiling
The important thing to establish initially is
that we know clinicopathologic factors alone,
such as tumour size and nodal status, are not
useful to use in isolation to determine risk of
late recurrence. Although there is a carry-over
© ASCO/Rodney White 2016
AMERICAN SOCIETY OF CLINICAL ONCOLOGY 2016 ANNUAL MEETING
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PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY