Rovalpituzumab tesirine ineffective against small cell lung cancer, confirm four studies

An accompanying editorial written by Dr. Dipesh Uprety, Dr. Jordi Remon, and JTO Editor Dr. Alex A. Adjei, discusses the recent history of the therapy's clinical trials and suggests some possible reasons why the drug has not been effective.

According to the editorial, SCLC remains a difficult disease to treat, especially at the time of relapse. Currently, topotecan is among the most effective, but it is not the most desirable and favored drug in the second-line setting because of its toxicity profile. Still, it has been difficult for new agents to "beat" this drug in the second-line setting. Several phase III clinical trials have failed to reveal improved survival over topotecan.

In 2017, clinicians were cautiously optimistic when Dr. Charles Rudin and colleagues published one of the first studies on rovalpituzumab tesirine in Lancet Oncology.

"The first in-human phase 1 clinical trial with Rova-T elicited significant enthusiasm because of the efficacy results--11 Of 60 assessable patients with pretreated SCLC who received an active dose of Rova-T achieved a confirmed response for an objective response rate (ORR) of 18%, tumors with high DLL3 expression (50% expression on tumor cells), the ORR was 38%. In a post hoc analysis, the ORR did not differ between those treated in the second- or third-line setting," according to the editorial.

But the four studies published in this month's JTO demonstrates that rovalpituzumab tesirine could not displace topotecan as an effective therapy for SCLC.

In one study published in the JTO—"Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study," lead author Dr. Fiona Blackhall, The University of Manchester, Manchester, United Kingdom, concluded that "compared with topotecan, which is the current standard second-line chemotherapy, Rova-T exhibited an inferior overall survival and higher rates of serosal effusions, photosensitivity reaction, and peripheral edema in patients with SCLC."

A second study published in JTO, "A Phase 1–2 Study of Rovalpituzumab Tesirine in Combination With Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Extensive-Stage SCLC," the researchers, led by Dr. Jyoti Malhotra, Rutgers Cancer Institute of New Jersey, New Brunswick, N.J., found that "Despite encouraging antitumor activity in previously treated ES SCLC, combination therapy with Rova-T and nivolumab plus or minus ipilimumab was not well tolerated at the dose levels and administration schedules evaluated."