Cancer patients are living increasingly longer thanks to new breakthrough medicines and perhaps the most important of these drugs are PD-1 inhibitors, PARP inhibitors, and gene therapies. These three classes of drugs are different, but each helps restore the body's ability to destroy cancer cells and thus offers cancer patients a chance of living longer.
Big strides in cancer outcomes
Some cancers remain incredibly difficult to treat, but generally speaking, new drugs are improving overall survival rates across most cancer indications.
According to the National Cancer Institute's annual report on cancer, death rates have decreased for 11 of the top 16 cancers in men and 13 of the top 18 cancers in women between 2000 and 2014, the latest year for which data was available. In this period, overall cancer death rates fell by an average of 1.8% annually for men and 1.4% annually for women.
In men, the biggest strides have been made in lung and bronchus cancer, which has seen mortality rates fall by an average 3.5% per year. In women, the biggest improvement in mortality has been the 2.8% decline for patients with colorectal cancer.
Although we're making significant advances in survival across many cancers, mortality rates have worsened in some cancers, such as liver cancer, and overall, five-year survival rates remain too low. For instance, the survival rate across all cancers is only 66% and that suggests that there still remains a need for revolutionary new cancer treatments.
A big advance in immuno-oncology
One of the biggest recent advances in cancer treatment could be the approval of a class of drugs called programmed cell death protein-1 (PD-1) inhibitors. These drugs keep cancer cells from hijacking the PD-1 pathway that's used by healthy cells to tell the immune system's T cells to leave them alone.
The first PD-1 inhibitors to win FDA approval were Bristol-Myers Squibb's (NYSE:BMY) Opdivo and Merck & Co.'s (NYSE:MRK) Keytruda. Initially, those drugs were green-lighted by the Food ad Drug Administration for use in melanoma, the fifth most common form of cancer in the United States, but since then, their ability to unleash the immune system to destroy cancer cells has led to approvals in a variety of cancer types, including lung cancer and kidney cancer.
At the onset, approvals for Opdivo and Keytruda were for their use in advanced cancer patients who no longer respond to other treatment options, but these drugs are increasingly advancing into earlier lines of therapy as trials demonstrate their effectiveness. For instance, Keytruda was approved as a first-line treatment in some lung cancer patients in 2016 and in 2017, and as a first-line treatment alongside chemotherapy for all metastatic non-small cell lung cancer patients. That first-line approval followed clinical trials showing that adding Keytruda to chemotherapy nearly doubled overall response rates versus chemotherapy alone.
The ability of PD-1 inhibitors to shrink tumors and delay disease progression across a variety of cancers has unleashed a flurry of studies that are evaluating them alongside other existing and clinical-stage medications. According to the Cancer Research Institute (CRI), 469 new combination trials were started in 2017 alone, and those trials hope to enroll more than 52,000 patients. Given all the activity, it's little wonder PD-1 drugs are among the most significant recent advances in fighting cancer.
Keeping cancer cells from repairing themselves
Drugs targeting poly (ADP-ribose) polymerase (PARP) are also helping patients battle back more effectively against cancer. An enzyme, PARP helps repair damaged DNA in cells, and while that's a good thing in healthy people, it can be bad news for cancer patients.
To prevent PARP from repairing DNA breaks in cancer cells, AstraZeneca (NYSE:AZN) developed Lynparza, a PARP inhibitor (PARPi) that secured approval in 2014 for use in advanced ovarian cancer treatment. The five-year survival rate in ovarian cancer is 92% when it's caught early. However, it's only 17% for stage IV ovarian cancer patients.
Lynparza's advanced ovarian cancer approval was supported by trials showing that 34% of patients responded to it for an average of 7.9 months. At first, it was only approved for patients who'd seen their disease return following three or more prior treatments, but its approval was expanded in August 2017 to include its use as a maintenance therapy. When used as a maintenance therapy, Lynparza reduced disease progression or death by 70% in one trial and by 65% in a second trial. It also improved median progression-free survival and median overall survival.
Lynparza isn't the only PARPi that's effective in ovarian cancer, either. Tesaro's (NASDAQ:TSRO) Zejula and Clovis Oncology's (NASDAQ:CLVS) Rubraca have also won FDA approval for use following trials that demonstrated their ability to prevent PARP from repairing DNA-damaged cancer cells.
Although ovarian cancer has been the focus of PARPi's so far, the FDA-approved Lynparza for use in some breast cancer patients in January. Specifically, Lynparza can help metastatic breast cancer patients with mutations to BRCA, another cell repair gene. Because breast cancer is the most common cancer in the U.S., with 252,710 people newly diagnosed annually, and about 5% to 10% of breast cancer patients have a BRCA mutation, far more people are likely to benefit from PARPi soon. PARPis are also being evaluated for pancreatic cancer, triple-negative breast cancer, and metastatic prostate cancer. If those trials succeed, then PARPi could become some of the most commonly used cancer drugs.
Gene therapy: the next big thing
PD-1s and PARPis are exciting new drugs, but it's gene therapy that may deliver the biggest improvement in mortality in the coming decade.
Last year, the FDA approved the first gene therapies for use in cancer patients: Novartis' (NYSE:NVS) Kymriah and Gilead Sciences' (NASDAQ:GILD) Yescarta. The two are chimeric antigen T-cell receptor (CAR-T) therapies that reengineer patient T cells so that they can better find and destroy cancer cells.
Here's how they work. A patient's T cells are removed and shipped to an offset lab where a virus is used to insert genetic code that allows them to spot and bind to CD19, an antigen commonly expressed by B-cell cancers, including leukemia and lymphoma. Then, these retrofitted cells are returned to the patient, where they multiply, find, and kill cancer cells.
Crafting these therapies is undeniably complex and it can take 20 days or longer to get engineered T cells back into a patient, but the results appear to be worth the wait. An 83% overall remission rate during its trials resulted in Kymriah's August 2017 approval in refractory, acute lymphoblastic leukemia (ALL). Similarly, the FDA's approval of Yescarta in diffuse large B-cell lymphoma was based on a 51% complete remission rate in its trials.
The prospect of gene therapy isn't limited to those cancers, either. In December, bluebird bio (NASDAQ:BLUE) reported data from a trial showing a 94% response rate to its CAR-T targeting multiple myeloma, bb2121.
If trials in other cancer types deliver similar efficacy, then gene therapies could dramatically change the outlook for cancer patients.
The quest for a cure
PD-1 drugs, PARPis, and gene therapies offer new hope to high-risk patients. Their use puts us steps closer to turning cancer into a chronic disease. The Holy Grail of cancer drug development, however, would be a functional cure. We're still far from delivering on that auspicious goal, but these revolutionary treatments show that we're making progress and that's something everyone can cheer.