乌鸦传媒

CHICAGO -- Investigators are hoping that an investigational treatment for recurrent small cell lung cancer (SCLC) will be the first therapeutic advance in 4 decades, after promising efficacy in an early trial.

Survival in SCLC -- no more than 15%, 2 years after diagnosis -- hasn't changed in 40 years and only one drug is approved to treat recurrent disease, according to of Memorial Sloan Kettering Cancer Center in New York City.

That could change if further study bears out the promise of rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate that targets a protein associated with the tumor cells, Rudin told reporters at the American Society of Clinical Oncology annual meeting.

The compound is "the first biomarker-directed treatment in small cell lung cancer," Rudin said.

While so-called targeted therapies have changed the landscape of other cancer subtypes, none has been tested before in SCLC, Rudin told 乌鸦传媒, largely because few targets were known.

Rudin noted that in many cancer subtypes, the key mutations lead to a gain of function -- something that can be inhibited by a drug. But in SCLC, the key mutations usually lead to a loss of function and are more difficult to target, he said.

But in SCLC, a proportion of tumor cells display Delta-like protein 3 (DLL3), which is not seen on the surface of normal cells, making it a possible therapeutic target, he said.

The investigational drug is a combination of an antibody that binds to DLL3, rovalpituzumab, and a substance toxic to the tumor cells, tesirine.

To begin testing the molecule in patients, Rudin's group enrolled 74 people with SCLC who had failed at least one previous line of therapy, and studied the safety and efficacy of the drug.

If more than half of tumor cells in a patient expressed DLL3, the cancer was classified as DLL3-high; some 67% of tested patients reached that level, Rudin reported.

The safety of the molecule was generally good and adverse effects manageable, he said. The most common severe toxicities were thrombocytopenia and serosal effusions, seen in 12% and 11% of patients, respectively.

Rudin cautioned that the study is very early -- it's the first time the drug has been used in people -- so efficacy results should be looked at with caution.

That said, 18% patients had a confirmed response regardless of the level of DLL3 expression, and the rate among those who were DLL3-high was 39%.

The confirmed clinical benefit rate -- stable disease or better -- was 89% in patients who were DLL3-high and 68% overall, he reported.

And the 1 year-overall survival was 32% in DLL3-high patients and 18% overall.

All the results compared very favorably to treatment with topotecan (Hycamtin), which is the only FDA-approved drug for second line treatment of the disease, Rudin said, and justify moving into later-stage trials, some of which are already under way.

"I'm optimistic," Rudin told 乌鸦传媒.

Patients with SCLC have been largely left out of the increasing understanding of the biology of cancers, commented , of the Helen F. Graham Cancer Center in Wilmington, Del.

"Small cell lung cancer has been a bit of a lost child," he told reporters.

But finding a target and a drug to attack that target are important steps forward. "Even though these improvements are small, they are advances," he said, in a field that has had little to cheer about for decades.

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