From OncoLog, August 2012, Vol. 57,
New Antibody Treatment Produces Responses in Patients with Advanced Cancer
A novel antibody treatment produced both tumor regression and disease
stabilization in patients with a variety of advanced cancers in a
recent phase I clinical trial.
In this multicenter trial, patients who had experienced disease
progression after standard systemic therapy for advanced or metastatic
cancer were treated with an antibody against the programmed death
ligand 1 (PD-L1) protein. The anti–PD-L1 monoclonal antibody was given
as an intravenous infusion every 14 days in 6-week cycles for up to 16
The new antibody produced complete or partial tumor responses in 17 of
135 evaluable patients: 9 with melanoma, 5 with non–small cell lung
cancer, 2 with kidney cancer, and 1 with ovarian cancer. And 8 patients
had responses lasting 12 months or longer. These results were
consistent with preclinical studies that indicated the anti–PD-L1
antibody enhances the immune cells’ ability to destroy tumors.
The programmed death 1 (PD-1) protein is a T cell co-inhibitory
molecule whose ligand, PD-L1, can be overexpressed in certain cancer
cells. PD-L1 expression in cancer cells allows them to evade
destruction by T cells. The new antibody therapy targets PD-L1 and
inhibits its interaction with PD-1, thus enhancing antitumor immunity
by allowing activated T cells to destroy the cancer cells.
Although other monoclonal antibodies targeting immune checkpoints have
been previously tested, the anti–PD-L1 antibody had fewer and less
severe adverse effects. Furthermore, the non–small cell lung cancer
responses to the anti–PD-L1 antibody were unexpected because, unlike
melanoma or kidney cancer, non–small cell lung cancer typically is
unresponsive to immunotherapy. The durability of the responses in
multiple tumor types was also unusual.
Taken together, these results indicate that the anti–PD-L1 antibody
could be a safe and useful immunotherapy against a variety of advanced
cancers. A new phase I trial under way at The University of Texas MD
Anderson Cancer Center and other institutions is enrolling patients
with refractory breast cancer and gastric cancer in addition to those
with the cancer types treated in this study.
The study’s report was published in the June 2 issue of the New England Journal of Medicine.
Accelerated Partial-Breast Brachytherapy Associated with Decreased
Long-Term Breast Preservation and Increased Complications Compared with
Compared with standard whole-breast irradiation (WBI), accelerated
partial-breast irradiation (APBI) in the form of brachytherapy is
associated with a decreased likelihood of long-term breast
preservation, according to a recent study. In this retrospective study,
researchers at MD Anderson analyzed Medicare claims data from 2003 to
2007 from 92,735 women nationwide who were 67 years or older and had
been diagnosed with invasive breast cancer and treated with lumpectomy
followed by radiation therapy. Compared with patients treated with WBI,
patients treated with brachytherapy had higher rates of subsequent
mastectomy (2.18% and 3.95%, respectively) and complications such as
soft tissue infection, hemorrhage, non-healing surgical wounds, rib
fracture, and fat necrosis. Of the complications analyzed, only
pneumonitis occurred more often in patients who had received WBI.
|“Women treated with APBI had about twice the rate of subsequent mastectomy, most likely because of tumor recurrence or local complications.”
|– Dr. Benjamin Smith
“We found that women treated with APBI had about twice the rate of
subsequent mastectomy, most likely because of tumor recurrence or local
complications, as well as higher rates of postoperative and
radiation-related complications,” said Benjamin Smith, M.D., an
assistant professor in the Department of Radiation Oncology and
corresponding author of the study’s report, which was published in the
May 2012 issue of Journal of the American Medical Association.
Dr. Smith pointed out that although these differences were significant,
both techniques were associated with low rates of local recurrence. He
said this retrospective study was important because previous studies
had not compared clinical outcomes of the two techniques in older
patients. Long-term data from prospective trials of the two techniques
will not be available for several years.
One such study already under way at MD Anderson and other institutions
is a randomized clinical trial in which treatment outcomes and effects
of APBI will be compared with those of WBI in patients 18 years and
Circulating Tumor Cells Have Predictive Value in Early-Stage Breast Cancer
Circulating tumor cells (CTCs)—cancer cells detectable in the blood—are
known to predict disease progression in patients with metastatic breast
cancer. And CTCs have now been shown to predict post-therapy relapse in
patients with early-stage breast cancer.
In a prospective study, researchers at The University of Texas MD
Anderson Cancer Center collected blood samples from 302 patients just
before definitive surgery for stage I, II, or III breast cancer. None
of the patients had undergone preoperative chemotherapy; about
two-thirds of the patients received postoperative chemotherapy. The
mean age of patients enrolled in the study was 54 years; the median
follow-up time was 35 months.
|“25%–35% of those women will have evidence of metastatic disease, and we wanted to understand why.”
|– Dr. Anthony Lucci
The CTCs were measured in the blood samples using the Veridex
CellSearch System and reported as the number of CTCs/7.5 mL blood. The
researchers found one or more CTCs in samples from 73 patients (24%);
29 patients (10%) had two or more CTCs, and 16 (5%) had three or more.
Detection of one or more CTCs predicted decreased rates of 2-year
progression-free survival. Eleven (15%) of the 73 patients with one or
more CTCs experienced a cancer relapse, compared with 7 (3%) of the 229
patients with no CTCs. An increased number of CTCs was also associated
with lower rates of overall survival. At 2 years, the overall survival
rates for patients with one or more, two or more, and three or more
CTCs were 94%, 89%, and 81%, respectively, compared with a 99% rate for
patients with no CTCs.
“There are a significant number of nonmetastatic breast cancer patients
for whom you remove their tumor, take out the lymph nodes, treat them
with systemic therapy, and render them free of any evidence of disease.
However, around 2 years later—a peak time for recurrence—25%–35% of
those women will have evidence of metastatic disease, and we wanted to
understand why,” said principal investigator Anthony Lucci, M.D., a
professor in the Department of Surgical Oncology.
Dr. Lucci said the results of the study, which were published in Lancet
Oncology, will need to be validated by a larger study before they can
affect clinical decision making about systemic therapy in early-stage
For more information, talk to your physician, visit www.mdanderson.org, or call askMDAnderson at 877-632-6789.
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