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Rovalpituzumab tesirine demonstrates activity in recurrent, refractory small cell lung cancer
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CHICAGO — Patients with progressive small cell lung cancer after previous therapy demonstrated delayed tumor growth and tumor shrinkage when treated with rovalpituzumab tesirine, according to results of a first-in-human study of the drug presented at the ASCO Annual Meeting.
Rovalpituzumab tesirine (SC16LD6.5, Stemcentrx) is a first-in-class antibody drug conjugate comprised of a humanized monoclonal antibody against DLL3 — a dipeptide linker expressed in approximately 80% of small cell lung cancers — and a pyrrolobenzodiazepine dimer toxin.
Charles M. Rudin
“These data need to be approached with caution due to the nature of the small cohort, but these data appear to be promising,” Charles M. Rudin, MD, PhD, medical oncologist and chief of the thoracic oncology service at Memorial Sloan Kettering Cancer Center, said during a press briefing.
Small cell lung cancer remains one of the deadliest malignancies, with a median survival of approximately 9 to 10 months from the time of diagnosis of metastatic disease. Topotecan is the only FDA–approved drug for recurrent disease.
Rudin and colleagues evaluated the safety and efficacy of rovalpituzumab tesirine in 74 patients with small cell lung cancer whose disease worsened after receipt of at least one prior therapy.
Patients were assigned doses ranging from 0.05 m/kg to 0.8 mg/kg; however, after researchers deemed doses above 0.4 mg/kg intolerable, they enrolled expansion cohorts in which patients received 0.2 mg/kg every 3 weeks and 0.3 mg/kg every 6 weeks.
The efficacy analysis included the 60 patients who were treated with doses between 0.2 mg/kg and 0.4 mg/kg.
Overall, 11 (18%) of those patients achieved a response and 41 (68%) patients achieved clinical benefit.
Researchers also retrospectively tested available archived tissue specimens for DLL3 expression. They found nearly all of the responders had elevated levels of DLL3.
Twenty-six patients had high DLL3 expression, defined as DLL3 in 50% or more of tumor cells. Ten (39%) of these patients responded to treatment, and 89% achieved clinical benefit. Median OS of this cohort was 5.8 months, and 32% achieved 1-year OS.
Researchers then evaluated responses according to whether patients were receiving rovalpituzumab tesirine as second-line or third-line treatment. Results showed patients with high DLL3 expression on the third-line treatment had a particularly high confirmed response rate of 50%, whereas historical response rates to conventional chemotherapy are only 18%. Further, 1-year OS rate was 33% in the rovalpituzumab tesirine group compared with 12% in historical data.
Researchers noted there is currently no approved third-line treatment for small cell lung cancer.
Toxicity appeared manageable. The most common grade 3 or worse treatment-related adverse events were serosal effusions (14%), thrombocytopenia (12%) and skin reactions (8%).
“Treatment options for patients with small cell lung cancer are limited,” study author Ramaswamy Govindan, MD, professor of medicine, Anheuser Busch chair in medical oncology and director of the medical oncology section at Washington University School of Medicine in St. Louis, told HemOnc Today. “These results are promising. If confirmed in future studies, this treatment approach would represent an entirely a new form of therapy for patients with small cell lung cancer.” – by Nick Andrews
Reference :
Rudin CM, et al. Abstract 8505. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclosure: Rudin reports consultant/advisory roles with AbbVie, AVEO, Boehringer, Ingelheim, Celgene, GlaxoSmithKline, Merck and Novartis and research funding from BioMarin.
Perspective
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Gregory Masters, MD, FACP, FASCO
Oncology has recently seen an advancement in the understanding of the molecular biology of tumor growth. Now the key is to bring those advances into small cell lung cancer. Even though improvements in survival may be small, they are advances. The importance is to recognize that we may have found a target and have developed a treatment for that target, and now we need to involve academic centers and training physicians and treated these patients on clinical trials.
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