Late-Breaking Clinical Trials: Potential New Therapies for Lymphoma, Prostate, and Other Cancers

June 2012, Vol 3, No 4

Chicago, IL—Several presentations featured at a news conference at the 2012 American Association for Cancer Research meeting highlighted new therapies showing promising results in the early stage of research, potentially charting new options for patients with cancer.

Ibrutinib for B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) represents 40% of all non- Hodgkin lymphoma. Some 23,000 new cases are diagnosed and 10,000 deaths occur annually in the United States, with a 50% cure rate at best, using chemotherapy and radiation therapy.

The B-cell receptor is required for survival of malignant cells in the activated B-cell–like (ABC) subgroup, which is 1 of 2 subgroups of DLBCL. The National Cancer Institute’s (NCI) Center for Cancer Research used geneexpression profiling to dissect this cancer into molecularly and clinically distinct subgroups.

Preliminary results from a phase 2 trial in patients with relapsed/refractory ABC DLBCL showed that the drug ibrutinib (PCI-32765) was effective for this patient population and well tolerated, according to principal investigator Louis M. Staudt, MD, PhD, a senior investigator with the NCI.

The response was rapid and encouraging. One patient with primary refractory disease had nearcomplete response at week 3, as confirmed by computed tomography and positron-emission tomography scan. Another patient has had 16 months of sustained remission, without side effects. A third patient showed significant, but not complete, response. The trial is ongoing.

New Developments in Prostate Cancer

Anthony M. Joshua, MD, MBBS, medical oncologist, Princess Margaret Hospital, Toronto, Canada, described the ANIMATE trial, a phase 2 openlabel assessment of neoadjuvant intervention with metformin to interrupt tumor-expression signaling in patients with prostate cancer. The ANIMATE trial is based on the notion that metformin lowers blood insulin, stresses cancer cells, and inhibits the mTOR pathway, which regulates tumor-cell growth, proliferation, and survival. Analysis of tumor samples suggests that metformin is active in depressing prostate-specific antigen (PSA) levels.

Results from ARMOR, a phase 1 trial of men with refractory, castrationresistant prostate cancer, were presented by R. Bruce Montgomery, MD, Associate Professor of Medical Oncol - ogy at the University of Washington School of Medicine, Seattle. The ARMOR trial is investigating the safety of galeterone (TOK-001), an oral, small-molecule drug with 3 mechanisms of action. The study included 48 patients who were chemotherapynaïve; results showed a ≥30% decline in PSA levels and varying degrees of tumor reduction, without significant adverse events. A phase 2b trial is planned for this year.

In yet another study, Reinhold Vieth, PhD, Professor, Department of Nutritional Sciences, and Department of Laboratory Medicine and Patho - biology, University of Toronto, Canada, and Director, Bone and Mineral Laboratory, Pathology and Laboratory Medicine, Mount Sinai Hospital, discussed his study investigating whether the rise in serum vitamin D depresses cellular proliferation of Ki67, a nuclear protein associated with cellular proliferation.

It has been documented that vitamin D3 slows the rise in PSA levels in men with prostate cancer, and that this increase is also slower in the summer months, when sunlight affects levels of the vitamin. Interim results suggest that vitamin D is safe in this patient population, and that it raises levels of calcitriol, which is related to lower Ki67 levels. Rising levels of vitamin D were also associated with higher levels of tumor-suppressive microRNA. Dr Vieth noted that these early results justified a larger study to examine whether vitamin D may prolong survival of patients with cancer or possibly even prevent cancer.

Other New Therapies

Refractory tumors of the Ewing sarcoma family (bone or soft tissue) in heavily pretreated patients were treated with a combination of the insulin-like growth factor-1 receptor antibody cixutumumab and the mTOR inhibitor temsirolimus, reported Aung Naing, MD, Assistant Professor, Department of Inves - tigational Cancer Therapeu tics, Division of Cancer Medicine, M.D. Anderson Cancer Center, Houston, TX.

In this trial, benefit was demonstrated in 29% of the patients, and 2 patients achieved complete remission. Most patients tolerated the treatment well and were able to maintain their performance status. Adverse events, such as myelosuppression, were a problem, but because of the drug’s efficacy, Dr Naing suggested managing the toxicity and keeping the patient on treatment.

Finally, John H. Farley, MD, Professor, Division of Gynecologic Oncology, Creighton University School of Medicine at St Joseph’s Hospital and Medical Center, Phoenix, AZ, described an openlabel phase 2 trial of selumetinib (AZD6244) in women with recurrent low-grade serous carcinoma of the ovary or peritoneum. This drug inhibits MAPK kinase 1/2, which is particularly active in this cancer. The trial that includes 52 patients suggests that selumetinib is active on tumors with minimal toxicity; a 15% response rate was observed. A randomized phase 3 trial has been proposed.—RH

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