NEW ERA

Recent advances in cancer research and treatment mean more favorable outcomes for patients.

BY JOANN GUIDRY

Combination Therapy

According to the American Society of Clinical Oncology, United States cancer death rates have declined 20 percent from their peak in 1991 (215.1 per 100,000 population) to 2010 (171.8 per 100,000 population). Today, there are a record 14.5 million cancer survivors in the United States. The ASCO attributes these statistics to ongoing clinical cancer research, resulting in prevention, earlier diagnoses and more effective treatments. Over the past decade, more than 60 anticancer drugs have been approved by the FDA. Combination therapy has shown itself to be more effective than a singular approach. Tumor biology research has led to the development of molecularly targeted drugs aimed at especially difficult-to-treat cancers. Immunotherapies have emerged to tackle cancers, such as advanced melonoma, lung cancers, certain blood cancers and solid tumors.

The ASCO recently named the treatment transformation for chronic lymphocytic leukemia (CLL) as the Cancer Advance of the Year. Nearly 120,000 Americans are living with CLL, the most common form of adult leukemia, and there had previously been few effective treatment options, but now there are four newly approved therapies for CLL. Obinutuzumab and ofatumumab, used in combination with standard chemotherapy, are two new immunotherapy drugs for previously untreated CLL. Ibrutinib and idelalisib are two molecularly targeted drugs for treatment-resistant or relapsed CLL. These new treatments are expected to dramatically improve the outlook for CCL patients.

BRAIN CANCER: For slow-growing glioma brain tumors, radiotherapy has been the standard first-line treatment for more than three decades. A study of 250 patients with glioma showed that adding chemotherapy to radiotherapy extended patient survival by 5.5 years compared to using only radiotherapy. Patients treated with radiotherapy alone survived on average 7.8 years; those treated with radiotherapy and a chemotherapy drug regime (procarbazine, lomustine and vincristine) lived 13.3 years. Combination treatment also resulted in a 10-year delay in disease progression,

Targeted Therapy

compared to a four-year delay with radiotherapy alone.

PROSTATE CANCER:

1950s, treatment for advanced prostate cancer has been androgen-deprivation therapy (ADT). While initially effective, prostate cancer often becomes resistant to ADT; chemotherapy then would be used only after this occurred and the disease worsened. But in a study of 790 men who were treated with both ADT plus chemotherapy at the same time, the men lived on average 10 months longer than with ADT treatment solely.

Targeted therapy blocks the growth and spread of cancer cells while limiting damage to healthy cells. This is accomplished because the treatment targets specific molecules in or on cancer cells or in the tumor’s immediate surroundings.

LUNG CANCER: More than 150,000 people die each year in the United States from lung cancer, accounting for nearly a third of all cancer deaths. Targeted therapies using the drugs erlotinib, afatinib and sometimes crizotinib have become the standard first-line treatment for those with nonsmall-cell lung cancer (NSCLC). All three drugs are initially effective with tumor shrinkage in close to two-thirds of patients. But all patients eventually develop resistance, and the cancer starts growing again usually within a year in about half of the patients. Researchers have been developing next-generation drugs to specifically target the genetic mutations that cause drug resistance. Two recent phase 1 clinical trials tested a pair of experimental drugs, AZD9291 and CO-1686, to combat the resistance mutation. Encouragingly, tumor shrinkage was seen in 50 to 60 percent of the studies’ participants. Longer-term followups will show if the drugs lead to overall survival improvement.

Immunotherapy

Immunotherapy treatment is designed to boost the body’s natural immune defenses against cancer. Types of immunotherapy include antibodies, cell-based and cancer vaccines. Materials made by the body or in a laboratory are utilized to improve, target or restore immune system function. Immunotherapies can stop or slow the growth of cancer cells, prevent cancer from spreading to other parts of the body or aid the immune system’s e ectiveness at eliminating cancer cells.

MED14736; strong responses were reported in two-thirds of the patients treated. None of the drugs have yet gained FDA approval for lung cancer treatment. Although MK-3475 (pembrolizumab) has been FDA approved for advanced melanoma treatment.

MELANOMA: The annual incidence of melanoma, the most deadly form of skin cancer, has increased by more than 60 percent in the United States during the past 30 years. FDA-approved immunotherapy drug ipilimumab has been successfully used since 2011 for melanoma that has spread to other body sites or that can’t be surgically removed. A recent clinical trial showed that ipilimumab might also be effective for patients with an earlier stage of melanoma to prevent recurrence after surgery. In the study of 950 patients with stage III melanoma and high recurrence risk, ipilimumab decreased the relative recurrence risk by 25 percent compared with a placebo. Unfortunately, considerable adverse effects, such as skin rash and inflammation of the pituitary gland, thyroid and colon made it necessary to stop the treatment in about half of the study participants. Researchers will continue to monitor those patients who were able to continue to assess any longterm benefits.

LUNG CANCER: New immunotherapy targeted drugs are also being tested for treating lung cancer. The drugs act on the proteins that control the immune system’s ability to attack and kill cancer cells. The antibody drugs used in the study included MK-3475, nivolumab and

B-CELL ALL: Patients with B-cell acute lymphocytic leukemia, the most common type of ALL, have limited treatment options once their cancer becomes resistant to chemotherapy. Long-term survival rates are low even with intensive treatments such as hematopoietic stem-cell transplantation. But chimeric antigen receptor-modified (CAR) T-cell immunotherapy is showing promise in treating ALL. A one-time treatment, CAR T-cell therapy doesn’t require surgery. First, blood is pumped out of a patient’s body and sent through a machine that separates out T cells. Next, the blood is intravenously returned to the body. The patient then undergoes chemotherapy while the T cells are reprogrammed in the laboratory. These reprogrammed T cells start making proteins that allow them to find and attach to antigen molecules on cancer cells. When infused back into the patient, the reprogrammed T cells multiply thousands of times and eliminate cancer cells.

In a small study, 16 adults with relapsed or chemotherapy-resistant B-cell ALL were treated with a new 19-28z CAR T-cell therapy. Patients started responding to therapy as early as seven to 10 days after infusion, and complete cancer remission occurred in 88 percent of the participants. In another study, 20 children and adults with relapsed or treatment-resistant ALL were treated with CTL019 CART T-cell therapy. Of the 20 patients, 14 experienced complete remission. CTL019 received FDA breakthrough therapy designation in July 2014, allowing for additional clinical trials.

Sources: asco.org, cancer.org, cancerprogress.net, cancer.net