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ECC 2015: First Targeted Treatment for Small Cell Lung Cancer Shows Promise

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Key Points

  • Of the 48 tumor samples analyzed, 33 were positive for DLL3 (delta-like protein 3).
  • Among the 29 DLL3-positive patients treated at the maximum tolerated dose of Rova-T, 10 (34%) had a partial response and 9 (31%) had disease stabilization.
  • The duration of response among these patients was more than 178 days, with no cases of disease progression.

Small cell lung cancer (SCLC) is an aggressive disease that is difficult to treat and is frequently diagnosed only when it has metastasized. Five-year survival rates in SCLC, which accounts for about 14% of all lung cancers, are very low, at only 6%. Researchers presented novel findings (Abstract 7LBA) with important implications for treatment of SCLC at the 2015 European Cancer Congress.

M. Catherine Pietanza, MD, Assistant Attending Physician at the Memorial Sloan Kettering Cancer Center, reported on results from a phase I trial of a novel agent, rovalpituzumab tesirine (Rova-T, or S16LD6.5), in 79 patients with SCLC who had progressed after first-line or second-line therapy.

“While other cancers have multiple treatment options, there is only one agent approved in SCLC, and none available in the third-line setting; the outlook for these patients is dismal,” Dr. Pietanza said.

Study Details

The patients ranged in age from 44–81, with a median age of 62 years. They received escalating doses of Rova-T once every 3 weeks until toxicity reached a point at which the increase in dose needed to be stopped. The drug was designed to bind to DLL3 (delta-like protein 3), a protein that is highly expressed in approximately 70% of SCLCs.

“Of the 48 tumor samples we were able to analyze, 33 were positive for DLL3. Among the 29 DLL3-positive patients we could treat at the maximum tolerated dose of Rova-T, 10 (34%) had a partial response and 9 (31%) had disease stabilization. The duration of response among these patients was more than 178 days, with no cases of disease progression,” Dr. Pietanza reported.

Rova-T is an antibody drug conjugate consisting of three components—an antibody, a linker, and the active chemotherapy, or cytotoxic payload. The antibody portion of an antibody drug conjugate can recognize cell surface receptors specific to and that are overexpressed in cancer cells, allowing the delivery of the chemotherapy directly to the tumor. This means the treatment is more effective and also minimizes its exposure to normal cells, with a consequent reduction in toxicity.

Biomarker Identified

“The high response rate is exciting in itself, and above that we have been able to identify a biomarker for SCLC in DLL3-positive patients, thus enabling us to ‘target’ treatment in SCLC. The activity of the drug that we have seen is remarkable, and importantly, the durable, long-term responses are notable in such an aggressive disease where progression is normally very rapid,” said Dr. Pietanza.

Whereas the most common treatment for early-stage non–small cell lung cancer is surgery, SCLC is not usually diagnosed in time for this to be a viable possibility, and chemotherapy is the standard of care. Currently, standard first-line therapy is the chemotherapy combination etoposide/platinum, which is combined with radiation therapy to the chest in limited-stage disease, and second-line chemotherapy consists of topotecan. Because SCLC can spread quickly to the brain, cranial radiation therapy may also be given.

“The first-line therapy [for SCLC] has not changed for four decades, and there is no third-line treatment at present, so it is clear that Rova-T is likely to fulfill an unmet need for these patients. I would like to see additional, larger trials to develop it further in settings where there is a clear need in this disease. We are looking forward to further assisting in its development and to gaining a better understanding of its value in all cases of SCLC,” Dr. Pietanza concluded.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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