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ARTICLE OF THEMONTH
Longer-interval dosing of
zoledronic acid effective in
patients with bone metastases
JAMA
2017;317(1):48-58. AL Himelstein, JC Foster, JL Khatcheressian, et al.
Impact on metastatic breast cancer
By Reshma L. Mahtani
DO
T
he use of zoledronic acid in patients with metastatic breast cancer (MBC) with
bony metastases is crucial to prevent skeletal-related events, which have been
shown to occur in up to 50% of patients when untreated. Skeletal-related events
are defined as fractures, spinal cord compression, need for surgery or radiation to relieve
symptomatic disease, and hypercalcemia of malignancy. Bone metastases disrupt the
normal homeostasis between bone formation and resorption by promoting osteoclast
maturation and activity and increased bone resorption.
Bone is a common site of recurrence in breast cancer. Bony metastases significantly
impact quality of life; therefore, MBC patients should be offered bisphosphonate (or
RANK ligand inhibitor) therapy at diagnosis with bone metastases. However, these
therapies are not without potential side effects. A rare and serious complication is oste-
onecrosis of the jaw. Therapies are also associated with the need for monthly visits to
the infusion suite, which can be disruptive especially to a patient who would otherwise
not require these visits as she is not on chemotherapy. The option to dose zoledronic
acid less frequently without compromising efficacy is therefore an attractive alternative
for patients.
Dr Mahtani is a haematologist/medical oncologist and Assistant Clinical
Professor of haematology/oncology at the Sylvester Comprehensive
Cancer Center, Miami.
Radiation with or without antian-
drogen therapy in recurrent
prostate cancer
N Engl J Med
2017;376:417-428, Shipley WU, Seif-
erheld W, Lukka HR, et al, for the NRG Oncology
RTOG.
Take-home message
•
In this double-blind, placebo-controlled
trial involving 760 patients who had
undergone primary prostatectomy with
a lymphadenectomy and had disease
with a tumour stage T2 or T3, no nodal
involvement, and a detectable PSA level
of 0.2–4.0 ng/mL, overall survival at 12
years was 76.3% in the bicalutamide
group vs 71.3% in the placebo group;
death from prostate cancer was 5.8% vs
13.4% in the bicalutamide and placebo
groups, respectively.
•
The addition of 24months of antiandrogen
therapy with daily bicalutamide to salvage
radiation therapy resulted in significantly
higher rates of long-term overall survival
and lower incidences of metastatic
prostate cancer and death from prostate
cancer than radiation therapy plus
placebo.
Introducing Editor’s Picks, a new section featuring the most
recent top clinical trials in oncology and haematology
specially selected by the
PracticeUpdate Oncology
Editorial
and Advisory Board members.
Take-home message
•
This was a randomised, open-label phase III trial designed to assess whether
12-week dosing of zoledronic acid was noninferior to every 4-week dosing
in 1822 patients with bone metastatic breast cancer, prostate cancer, and
multiple myeloma. There was no significant difference between the rate of
skeletal-related events among patients who received zoledronate every 12
weeks and those who received it every 4 weeks.
•
The authors concluded that longer-interval treatment with zoledronic acid may
be an acceptable treatment modality among patients with bone metastases.
For patients who expressed <1% of PD-L1,
response was 16.1%. Grade 3–4 treatment-re-
lated adverse events occurred in 18%, with
three treatment-related deaths.
This is a novel study; once again it mirrors
response rates observed in previous studies
involving checkpoint inhibitors. Of particu-
lar interest, monotherapy with nivolumab is
beneficial regardless of whether PD-L1 is
expressed. However, perhaps most excitingly,
it heralds an era where individualised therapy
in bladder cancer can be based on molecular
marker expression. Much like oestrogen and
Herceptin receptor expression can influence
treatment paradigms in breast cancer, personal-
ised care is a reality for bladder cancer. Patients
can be directly counselled regarding potential
response rates and therapeutic strategies based
on PD-L1 expression. It remains to be seen
whether routine, efficient and cost-effective
PD-L1 expression is clinically applicable.
also await the results of the RADICALs and
GETUG-16 (salvage radiation trials) to assess
if practice should change.
EDITOR’S PICKS
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VOL. 2 • NO. 2 • 2017