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 cycles.

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 Whole-Breast Irradiation

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.

“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 older.

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.

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 cancer patients.
 
For more information, talk to your physician, visit www.mdanderson.org, or call askMDAnderson at 877-632-6789.

Other articles in OncoLog, August 2012 issue:

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