FDA Approves Expanded Use of Nivolumab for Lung Cancer

In March of this year, the immunotherapy drug nivolumab (Opdivo®), made by Bristol-Myers Squibb, became the first immunotherapy approved by the FDA for the treatment of lung cancer that has stopped responding to chemotherapy. At that time, use of nivolumab was restricted to patients with a less common form of non-small cell lung cancer (NSCLC), called squamous type.

Today, the FDA expanded its approval of nivolumab to include patients with non-squamous NSCLC that has stopped responding to chemotherapy. Approximately 85% of NSCLC cases are the non-squamous type.

Nivolumab belongs to a class of immune-targeting drugs called checkpoint inhibitors. These are drugs that act to “release the brakes” on immune cells, allowing the immune system to mount a stronger and more effective attack on cancer. The particular immune “brake” targeted by nivolumab is called PD-1.

While the FDA’s approval was not unexpected, given encouraging results presented at this year’s ASCO meeting, the approval came three months earlier than expected—a sign perhaps of just how eager regulators were to get this drug into the hands of doctors treating patients who need other options.

Today’s approval was based on the results of a large phase III trial that showed that patients who received nivolumab lived an average of 12.2 months compared to 9.4 months for those receiving standard chemotherapy. What’s more, 19 percent of patients treated with nivolumab experienced complete or partial shrinkage of their tumors, an effect that lasted an average of 17 months, compared to only 12 percent of docetaxel-treated patients who experienced benefit for an average of six months.

The data from the trial also show that patients whose tumors make a protein marker called PD-L1 had better overall responses. Nivolumab nearly doubled overall survival for patients whose tumors were PD-L1 positive (more than 17 months compared to 9 months for docetaxel).

PD-L1 is a protein that binds to the PD-1 receptor on immune cells. Cancers often make PD-L1 as a way to ward off an immune attack. It makes intuitive sense that tumors making PD-L1 would respond better to anti-PD-1 therapy, since this drug acts to release the same brake that the cancer has engaged. But even patients with PD-L1-negative tumors still benefit from the therapy, so nivolumab is approved for these patients too.

“There is still a lot to learn about the PD-1/PD-L1 pathway and its effects in lung cancer, as well as other tumor types,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research in a press release. “While Opdivo showed an overall survival benefit in certain non-small cell lung cancer patients, it appears that higher expression of PD-L1 in a patient’s tumor predicts those most likely to benefit.”

Nivolumab is the second PD-1 immunotherapy to be approved for lung cancer in the past week. On Friday, the FDA approved pembrolizumab (Keytruda®) for patients with PD-L1-positive NSCLC that has stopped responding to chemotherapy.

Some of the earliest lung cancer patients treated with nivolumab have spoken publicly about their positive experiences on the drug. Pam Griffith, 66, of Florida, achieved a full remission of her advanced lung cancer that failed to respond to chemotherapy. “I would not be alive today if it were not for this drug,” she said in interview conducted last year; she is still alive and free of disease today.

Maureen O’Grady, 62, of Connecticut, whom we featured in a CRI-sponsored video in June, was also quick to express her gratitude. “There are so many milestones I‘ve been blessed to witness and attend thanks to this immunotherapy,” said O’Grady, who this year celebrated her 41st wedding anniversary and whose two grandchildren were not yet born when she was treated but who are now age 4.

Lung cancer is the leading cause of cancer-related deaths worldwide. More than 1.5 million people die each year of the disease, according the World Health Organization. NSCLC is the most common type of lung cancer, accounting for approximately 85% of cases. Lung cancer was once considered an unlikely target for immunotherapy, but recent experience with PD-1 checkpoint inhibitors has radically changed doctors’ views on the subject. More and more patients are alive and thriving thanks to these drugs, which would not exist without the support of grant-making bodies like the Cancer Research Institute and the dedicated scientists who have been studying the immune system and cancer for decades.