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FROM THE LITERATURE
Myeloma
A New Standard of Care in Multiple Myeloma?
Treatment with melphalan plus prednisone has been a standard of
care for non-transplant candidates with newly diagnosed multiple myeloma for more
than four decades. During the past 10 years, high-dose therapy with hematopoietic
stem-cell transplantation (SCT) has become the preferred therapy for patients under
the age of 65 years, but older patients and patients with significant co-existing
illnesses usually cannot tolerate this treatment. The median age at diagnosis of
myeloma is approximately 70 years, therefore more than half the patients with newly
diagnosed myeloma may not be eligible for high-dose therapy. For these patients,
improved treatment is needed.
Results of a phase III trial comparing melphalan + prednisone vs melphalan + prednisone
plus bortezomib (Velcade®) in this patient population (n=682) demonstrate that the
addition of bortezomib significantly improves the median time to progression (TTP),
the primary endpoint by 7.4 months (HR=0.48; p<0.001). The bortezomib group was
superior to the melphalan + prednisone for the following: partial response or better,
71% vs 35%; CR rate, 30% vs 4% (p<0.001); median duration of response, 19.9 months
vs 13.1 months; overall survival, HR of 0.61 (p=0.008).
This study demonstrates the superior efficacy of bortezomib plus melphalan and prednisone
compared to melphalan and prednisone alone for the front-line treatment of patients
who are 65 years of age or older and cannot receive more aggressive therapy. The
authors state that since superior efficacy in the treatment of myeloma has now been
shown with bortezomib or thalidomide in combination with melphalan and prednisone,
the two-drug combination should no longer be considered the standard of care in
patients 65 years of age or older.
San Miguel JF, et al. Bortezomib plus melphalan and prednisone for initial treatment
of multiple myeloma. N Engl J Med. 2008; 359: 906-17.
Breast Cancer
How Many Prognostic Tests Do We Need?
The September 1, 2008 issue of the Journal of Clinical Oncology
(JCO) includes an article and an accompanying editorial that address prognostic
tests for breast cancer. For the reader, several questions immediately come to mind:
Is one test “better” than the other(s)? Should we develop more tests to cover all
of the various factors involved? Is there an “ideal” prognostic test for breast
cancer?
- Currently two independently validated prognostic tests are
widely used,
Adjuvant! Online and the Oncotype DXTM recurrence score (RS)
assay. Adjuvant! is a mathematical algorithm that provides an estimate of risk of
breast cancer (BC) related death at 10-year follow-up based on the tumor size, the
number of involved nodes, and estrogen receptor (ER) status. Estimates of the efficacy
of therapy are based primarily on the proportional risk reduction (PRR) analysis
from the Oxford overview. The 21-Gene RS Assay, a genomic classifier, provides individualized
risk estimates based on measurement of the expression of 16 cancer-related genes
and has the potential to more accurately identify individuals who benefit from chemotherapy.
- The trial by Goldstein et al compared these two very different prognostic
tests in a retrospective study of BC patients with hormone receptor (HR) positive
disease and zero to three positive axillary nodes who received contemporary chemohormonal
therapy. It should be noted that the study population is quite different from the
originally intended clinical target population (ER+, axillary node negative BC treated
with tamoxifen) for RS assay. Result: RS was a highly significant predictor of recurrence,
in both node (-) and node (+) disease (p<0.001 for both). RS also predicted recurrence
more accurately than clinical variables when integrated by an algorithm modeled
after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate
was only 5% or less for the estimated 46% of patients who have a low RS (<18).
The 21-Gene RS Assay may be useful to select low-risk patients for abbreviated chemotherapy
regimens or high-risk patients for more aggressive regimens or clinical trials evaluating
novel therapies.
- The most significant information from this trial is that RS and
Adjuvant! are independent of each other with a modest concordance, BUT within each
risk category defined by Adjuvant!, RS provided additional prognostic information
and vice-versa. For the 43% of those who were in the low Adjuvant! risk group, the
risk of recurrence was increased 2.6-fold and 4.0-fold respectively for intermediate
and high RS. For the 30% of patients in the intermediate Adjuvant! risk group, the
risk of recurrence was increased 9.6-fold and 5.8-fold respectively for intermediate
and high RS. For the 24% of patients in the high Adjuvant! risk group, only high
RS was associated with a significantly increased risk of relapse (2.6-fold). It
is also clear that Adjuvant! can also provide additional information for risk groups
defined by RS. Thus the best scenario for a patient is to have a low RS score and
low risk according to Adjuvant!. If either of the two shows poor risk, then the
risk of relapse appears to be increased.
- Lastly, this study also demonstrated a need to integrate RS and
Adjuvant! into a single prognostic algorithm. There are some technical hurdles to
overcome, but new trials to implement this strategy are underway. So which test
is better? A combined approach appears to provide the best of both worlds.
Goldstein LJ, et al. J Clin Oncol 26: 4063-4071, 2008
Paik S. J Clin Oncol 26: 4058-4059, 2008
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