Immunotherapy Offers Melanoma Patients New Hope

Metastatic melanoma is one of the most difficult forms of cancer to treat, with survival rates as low as 15% for those with a stage IV diagnosis. These low survival rates began to improve with the 2011 approval of ipilimumab, the first checkpoint inhibitor. Checkpoint inhibitors work on T-cells and reactivate the immune system so it continues fighting cancer cells. Nivolumab is another checkpoint inhibitor that is also used to treat melanoma patients, alone or in combination with other medicines. A recent study at Dana Farber tested combining ipilimumab and nivolumab in patients with advanced melanoma who had not previously been treated. Results of the study showed that 53 percent of patients who received this combination of drugs were alive four years later, a remarkable result in melanoma clinical research.

The study followed 945 patients who had untreated and inoperable stage III or stage IV melanoma. They were separated into three groups, with one receiving the combination of nivolumab and ipilimumab, another receiving just nivolumab and the final group receiving just ipilimumab. Fifty-eight percent of patients treated with the two drugs had their cancer shrink, compared to only 45 percent of patients who received nivolumab alone and 19 percent for those who received ipilimumab alone. Additionally, several patients treated with the combination had their tumors disappear completely.

The median length of survival for patients varied greatly, ranging from 19.9 months in the ipilimumab group to a currently unknown number in the group treated with both drugs, because patients continue to do well and a median outcome cannot yet be established.

Treatment was given to patients in this study until they received the maximum clinical benefit, were experiencing unacceptable side effects or the patient asked to have treatment discontinued. For patients who survived four years, 71 percent of those treated with the drug combination were no longer receiving treatment along with 50 percent of the nivolumab group and 39 percent of the ipilimumab group being off treatment as well.

Patients who received the combination of drugs experienced a higher rate of adverse side effects — 59 percent — compared to 22 and 28 percent in the nivolumab and ipilimumab groups respectively. Despite these side effects, authors of the study believe this is an important discovery for melanoma patients and will improve long-term survival rates in the coming years.

Targeted Cancer Therapy

Since cancer involves the rapid reproduction of cells, most forms of treatment, like chemotherapy, target and kill rapidly dividing cells, regardless of whether or not they’re cancerous. Targeted therapy, also known as a form of precision medicine, is a new type of treatment that is becoming a focus in cancer research because it works on stopping and killing cancer cells without harming other cells, a common issue with chemotherapy.

Precision medicine involves treating a patient’s tumor based on the genetic change in the cancer cells (either in malignant blood cells or in the solid tumors themselves) and interfering with proteins that help cancers grow and spread. These medications work in a variety of ways to target the cancer, including helping the immune system destroy cancer cells, stopping the cancer cells from growing, killing the cancer cells and starving the cancer of stimulants (such as hormones)  it needs to reproduce and grow.

This therapy requires doctors to have a genetic understanding of the cancer and allows for more personalized treatment.  In some cancers like non-small cell lung cancer, forms of chronic leukemia, and types of breast cancer, these molecularly targeted therapies have become a standard of care.  It also is being studied in many clinical trials with extremely positive results. In order to receive these treatments, a patient must undergo a test to see if the genetic change being targeted is present in their tumor. This test is often a blood sample or a biopsy where the doctor removes a sample of the cancer and then the DNA is sequenced to look for genetic changes. If the changes match the targets of the therapy, the patient may be a good candidate to receive the drug. The results have been extremely promising and indicate that this may be an area where many new discoveries are made in the coming years. Several targeted medicines (such as ponatinib and brigatinib) have been approved and are widely used by patients whose cancers have been genetically defined.