FDA approves Amgen drug for persistent, deadly form of lung cancer

The Food and Drug Administration on Thursday approved an innovative new treatment for patients with a form of lung cancer. It should be used only by patients who have exhausted all other treatment options for small cell lung cancer and who have a life expectancy of four to five months.

The drug tarlatamab, or Imdelltra, made by the company Amgen, tripled patients’ life expectancy, giving them a median survival of 14 months after taking the drug. Forty percent of those who received the drug responded.

After decades without real progress in treatments for small cell lung cancer, tarlatamab offers the first real hope, said Dr. Anish Thomas, a lung cancer specialist at the Federal National Cancer Institute who has not participated in the trial.

“I feel like it’s a light after a long time,” he added.

Dr. Timothy Burns, a lung cancer specialist at the University of Pittsburgh, said the drug “is going to be a practice changer.”

(Dr. Burns was not an investigator in the study but served on an Amgen advisory board for another drug.)

The drug, however, has a side effect that can be serious: cytokine release syndrome. It is an overreaction of the immune system that can lead to symptoms such as a rash, rapid heartbeat, and low blood pressure.

Each year, approximately 35,000 Americans are diagnosed with small cell lung cancer and face a grim prognosis. The cancer has usually spread beyond the lung by the time it is detected.

The standard treatment is old-fashioned chemotherapy – unchanged for decades – combined with immunotherapies that add about two months to patients’ lifespan. But, almost inevitably, the cancer resists treatment.

“In 95 percent of cases it will come back, often within a few months,” Dr. Burns said. And when it comes back, he added, patients have a harder time tolerating chemotherapy, and the chemotherapy is even less effective.

Most patients only live eight to 13 months after their diagnosis, despite chemotherapy and immunotherapy. The group of patients participating in the clinical trial had already undergone two or even three cycles of chemotherapy, which is why their life expectancy without medication was so short.

The dismal prognosis of small cell lung cancer stands in stark contrast to the situation of the other, more common non-small cell lung cancer, which has been a triumph of the cancer treatment revolution. New targeted therapies seek out the molecules that cancers need to grow and contain their spread.

As a result, Dr. Thomas said, many patients with this form of lung cancer live so long that their disease becomes “almost like a chronic disease.”

There are several reasons why small cell lung cancer patients have been left behind.

One of them is the type of genetic mutation that cancer depends on to grow.

Dr. Jay Bradner, Amgen’s chief scientific officer, explained that other cancers are caused by aberrant genes being activated. Treatment involves medications to turn off these genes.

But small cell lung cancer is driven by disabled genes, making them difficult to target, Dr. Bradner explained. Another reason is cancer’s ability to block immune system cells that try to destroy it.

Tarlatamab is an antibody designed to overcome these obstacles. It has two arms, the first of which attaches to the growth-promoting molecule that stands like a flag on the surface of cancer cells. It serves as the drug’s identification tag, allowing tarlatamab to detect cancer cells. The other arm grabs a T cell floating in the bloodstream. The T lymphocyte, a white blood cell, can kill cancers if it can get close to them.

The drug brings T cells and cancer cells together, punching holes in the cancer or activating genes that cause it to self-destruct.

Patients participating in the clinical trial say they have their lives back.

Martha Warren, 65, of Westerly, RI, was diagnosed last year with small cell lung cancer. She joined Facebook groups and immediately saw the bad news: Most patients don’t live long. Her best hope, she decided, was a clinical trial. After chemotherapy and immunotherapy, as her cancer grew rapidly, she was accepted into the Amgen study and began traveling to Yale for infusions of the drug.

Almost immediately, his cancer began to shrink – dramatically.

“I feel as normal as I did before I had cancer,” Ms. Warren said. “There is a lot of hope with this drug,” she added.

The Amgen study and approval, however, involved patients like Ms. Warren who had already completed several rounds of treatment. Could tarlatamab help sooner?

Amgen is now beginning such a study, testing the drug right after initial chemotherapy.