Kidney cancer is one of several cancers that has responded well to immunotherapy drugs, which can free the immune system from restraints that cancer cells can impose on it. The drug nivolumab (Opdivo), for example, which was recently approved, can extend survival in patients with metastatic kidney cancer after other drugs have failed.
But can these immunotherapy agents play a role in earlier-stage disease, in patients who have had surgery and show no signs that their cancer has spread, but still face a risk of recurrence? That’s what Dana-Farber researchers are hoping to find out with a novel, large clinical trial.
“We want to find out if we can increase cure rates if we give immunotherapy along with surgery,” says Lauren Harshman, MD, co-director of the Kidney Cancer Center at Dana-Farber. She is principal investigator of a new international, National Cancer Institute-sponsored phase 3 trial called PROSPER, in which some patients with localized kidney cancer will receive the immunotherapy drug nivolumab before they have surgery, and then for nine months afterward.
Surgery to remove the tumor, along with part or all of the kidney, is standard treatment for most patients with kidney cancer. This will cure some, while others – especially those with more advanced disease – are likely to experience a recurrence within a few years from cancer cells left behind.
In some other forms of cancer, like breast cancer, patients who have had surgery often receive chemotherapy to rid the body of cancer cells that spread beyond the tumor. But chemotherapy hasn’t been effective for this purpose in kidney cancer.
In recent years, newer targeted drugs like sunitinib and sorafenib have improved survival in metastatic kidney cancer, leading researchers to wonder if these treatments might reduce recurrences if given to earlier-stage patients after surgery.
“It made sense to move these drugs earlier, following surgery, to see if we could eliminate the cancer cells that escaped,” explains Harshman.
But so far, clinical trials of the targeted drugs in such patients have been inconclusive. One trial, which used sunitinib and sorafenib, failed to find a benefit. A second has found that high-risk patients taking sunitinib gained about one year of disease-free survival over those given a placebo. But the results are still unclear, and these targeted drugs are also relatively toxic – one-third of patients stopped taking them because of side effects.
The PROSPER trial is a new strategy to see if immunotherapy can lower the chances of recurrence, while hopefully offering better quality of life. Nivolumab, a checkpoint inhibitor antibody, enhances the body’s immune response against the cancer by blocking regulatory molecules that tumors use to hide from the immune system. It is generally better tolerated, with fewer severe side effects than the targeted agents.
The PROSPER trial will enroll 766 patients with stage II or greater renal cell carcinoma, the most common form of kidney cancer. Harshman explains that patients will receive two doses of nivolumab prior to surgery, and then will continue to get the drug for nine months post-surgery. The up-front two doses, she says, aren’t expected to kill all the cancer cells, but to “prime” the immune system’s T cells – the main anti-cancer weapons – which may have initially swarmed to the tumor but weren’t effective. Harshman and her colleagues hope the nivolumab will stimulate the T cells “and build a T cell army.”
PROSPER researchers will be looking for an improvement in recurrence-free survival – how long the patients live without the disease returning – and overall survival in patients treated with nivolumab compared with those treated with surgery alone. They will also look for biomarkers – biological “signals” in the patients’ tumors that predict which individuals will respond better to the nivolumab treatment.
Beside the PROSPER study, Dana-Farber researchers are also preparing to treat some kidney cancer patients with a new type of personalized cancer vaccine called NeoVax, which was pioneered at Dana-Farber.