Opdivo® and Other Precision Cancer Medicines Advance The Treatment of Small Cell Lung Cancer
by C.H. Weaver M.D. 8/23/2018
The U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab) for the treatment of metastatic small cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy.1 Opdivo is the first new treatment approved for SCLC in over 20 years.
About Small Cell Lung Cancer
According to the American Cancer Society, more than 234,000 people will be diagnosed with lung cancer and 154,050 will die from the disease in 2018, making it the leading cause of cancer death. SCLC primarily is associated with smoking and accounts for about 10 to 15 percent of all lung cancers. In the United States, about 27,000 individuals with SCLC will be diagnosed in 2018. The survival for most SCLC patients is less than a year and there have been no recent advances in its treatment.2-5
Opdivo is a precision cancer medicine that belongs to a new class of medicines called PD-1 inhibitors that have generated great excitement for their ability to help the immune system recognize and attack cancer. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 may enhance the ability of the immune system to fight cancer. Opdivo works by blocking PD-1. PD-1 inhibitors are being investigated in more than 30 different cancers, and it is already approved for the treatment of melanoma and lung cancer and researchers continue to evaluate its effectiveness in different types of cancer.
The approval of Opdivo was based on data provided to the FDA from the ongoing CheckMate -032 study evaluating Opdivo in patients who experienced disease progression after platinum-based chemotherapy.1 Twelve percent of SCLC patients treated with Opdivo after platinum-based chemotherapy responded to treatment and among these responders, the average duration of response was 1 and a half years.1
About Precision Cancer Medicine
Not all cancer cells are alike: Cancer cells may differ from one another based on what genes have mutations. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. This “genomic testing” is performed on a biopsy sample of the cancer and increasingly in the blood using a “liquid biopsy”
Once a genetic abnormality is identified, a specific precision cancer medicine or targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. Opdivo directly attacks the PD 1 ligand enhancing the immune system to work better.
Another target is the poly ADP-ribose polymerase (PARP) enzyme which plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.
In another recent study doctors from MD Anderson Cancer Center enrolled 104 patients with relapsed SCLC from seven centers across the country. Patients were treated with either the PARP inhibitor veliparib combined with a standard oral chemotherapy regimen or the chemotherapy alone and directly compared.
Overall the combination therapy was well tolerated, and the researchers found that, the overall response to treatment was almost was three times higher in patients treated with the PARP inhibitor plus chemotherapy compared to chemotherapy alone.
Researchers also investigated biomarkers that might predict a response to PARP inhibitors and found that patients whose tumors expressed the elevated levels of SLFN11 experienced significantly delayed cancer progression and improved survival.
The doctors are now further evaluating PARP inhibitors as initial treatment and in higher doses. Advances in identifying precision cancer medicines have recently improved the outcomes in many kinds of cancer and now perhaps these advances will benefit individuals with SCLC, patients should inquire about the role of these newer medicines with the treating cancer physician.
Decision Resources Group Epidemiology Data. Burlington, MA: Decision Resources Group.