A widely used treatment called zoledronic acid (ZA) — approved by the FDA to reduce and delay bone complications caused by cancer that has spread to the bone — may now be given at intervals three times longer than the current standard with similar benefit, according to new results presented by Andrew L. Himelstein, M.D., a medical oncologist at Christiana Care’s Helen F. Graham Cancer Center & Research Institute, during the 2015 Annual Meeting of the American Society of Clinical Oncology.
“These findings support a potential practice change in our approach to treating bone metastases,” said Dr. Himelstein. “Lengthening the time period between doses will greatly improve the quality of life for our patients, including many who are highly symptomatic and find it a significant burden to make the monthly trips for treatment.” Fewer treatments and fewer office visits translate into lower costs and added value for patients.
Dr. Himelstein, along with co-investigators at seven institutions, tested 1,822 patients with bone metastasis from multiple myeloma or solid tumors, including breast and prostate cancer. Patients were randomized to receive either the standard course of therapy — intravenous ZA monthly for two years — or ZA administered at a longer interval, every three months for two years. Study results indicate that the longer dosing interval was comparable to standard dosing in relieving bone pain and preventing the incidence of skeletal-related events, defined as radiation therapy to bone, fractures, spinal cord compression, loss of function, or surgery to bone.
“There is some evidence that ZA persists in the body much longer than the three or four weeks between standard treatments,” said Dr. Himelstein. “Bone turnover markers were still lowered by ZA given every 12 weeks, indicating a persistent effect of ZA in the bone. That these levels are suppressed provides further evidence that ZA every 12 weeks is effective.”
Zoledronic acid is also approved for the treatment of high calcium levels caused by cancer and, in a slightly higher dose, as a once-a-year treatment for osteoporosis. These formulations of ZA were not part of this National Cancer Institute sponsored study, CALGB 7064, initiated by the Alliance for Clinical Trials in Oncology.
Promising new treatment for metastatic lung cancer
Christiana Care medical oncologist Michael J. Guarino, M.D., reported on mid-stage clinical trial results of an investigational targeted therapy, sacituzumab govitecan, that showed promising anti-tumor activity in patients with metastatic lung cancer. The two types of lung cancer are small cell (SCLC) and non-small cell (NSCLC), which is the most common.
Lung cancer is the second most commonly diagnosed cancer in the U.S. and the deadliest, killing more people than breast, colon and prostate cancers combined.
Sacituzumab govitecan is a leading antibody drug conjugate, developed by Immunomedics Inc., that combines a chemotherapy drug (SN-38) with a humanized antibody designed in the lab to target the Trop-2 receptor expressed by many solid cancers. SN-38 is the active metabolite of irinotecan (Camptosar) used to treat solid tumors, particularly metastatic colorectal cancer. This knock-out combination is capable of delivering 136 times more SN-38 than its parental drug directly to the tumor and thus minimizing harm to surrounding healthy tissue.
Patients with advanced stages of NSCLC are commonly treated with chemotherapy, targeted drugs or some combination of the two. For SCLC, which is the more aggressive lung cancer, treatment is limited to chemotherapy with or without radiation therapy. Five-year survival rates for both types of lung cancer are very low (2.7 to 3.7 percent).
In a multicenter study of 47 patients with metastatic lung cancer (25 NSCLC, 22 SCLC), treatment with sacituzumab govitecan produced tumor shrinkage of 30 percent or more in patients with NSCLC (32 percent) and SCLC (30 percent). For the 25 patients who responded to the study drug, all 11 SCLC patients and 12 of 14 NSCLC patients, or 86 percent, had a time-to-disease progression that was longer than their last therapy. These patients had previously failed a median of 2.5 (range 1-7) and 3 (range 1-8) cancer treatments, respectively. The study also showed that these heavily pre-treated lung cancer patients safely tolerated the drug.
“This is an interesting and unique delivery system of an effective third- or fourth-line cancer treatment with relatively low toxicity for lung cancer, a disease that is very difficult to treat,” Dr. Guarino explained. “The duration of response to this drug, offers a glimmer of hope for patients that they can feel better and live longer, even after trying other conventional therapies unsuccessfully. The study also holds promise that further testing of this drug could reveal additional benefit to patients.”
Following the Phase 2 trial, Immunomedics Inc. announced that the FDA has fasttracked development and review of sacituzumab govitecan for the treatment of NSCLC in patients who have failed two prior lines of therapy. The drug is already fast-tracked to treat SCLC and triple-negative breast cancer.
Medical Oncologist Gregory A. Masters, M.D., at the Helen F. Graham Cancer Center & Research Institute, also participated as a co-investigator in the study.
In 2014, the National Cancer Institute selected the Helen F. Graham Center & Research Institute to join its Community Oncology Research Program (NCORP), an elite network of cancer-fighting centers in communities throughout the United States. Enrollment in clinical trials at the Graham Cancer Center is well above the national average. Twenty-four percent of cancer patients enter a research clinical trial, compared with a national average of only 4 percent.
Community cancer programs like the Graham Cancer Center offer the potential of larger, more diverse patient enrollment that makes it more feasible to test new inventions and strengthens the ability to generalize study findings to an even broader population of cancer patients. Also, when community cancer specialists participate in these studies, more effective, evidence-based strategies become part of routine cancer care.