Luis Paz-Ares, MD, PhD
Liposomal irinotecan (Onivyde) achieved disease control in almost half of patients as a second-line treatment for small cell lung cancer (SCLC), according to findings from Part 1 of the phase II/III RESILIENT trial presented at the 2019 World Conference on Lung Cancer (WCLC).1,2
The agent induced an objective response rate (ORR) of 44% among 25 patients treated with the optimal dose of 70 mg/m2
. The ORR comprised 11 partial responses (PRs). The best overall response rate (PRs plus stable disease) was 72% (n = 18). The 12-week disease control rate was 48%. Sixty-eight percent of patients had some level of tumor shrinkage.
“Immunotherapies and combination therapies have proven beneficial in the first-line setting, but despite these advances, many small cell lung cancer patients rapidly relapse due to the aggressive nature of the disease,” Luis G. Paz-Ares, MD, PhD, lead investigator and chief physician, Hospital Universitario 12 de Octubre, Madrid, said in a press release.
“While the current standard of care in the second-line setting can extend survival, treatment toxicity has prevented some patients from receiving the full recommended dose. There is a clear need for more treatment options that may give more patients the chance to remain on therapy. It is positive that the RESILIENT trial will continue to investigate this,” added Paz-Ares.
The 2-part, open-label phase II/III RESILIENT study (NCT03088813) is exploring single-agent liposomal irinotecan in patients with SCLC with disease progression following a frontline platinum-based regimen. Part 1 of the trial involves dose-finding and dose-escalation analyses and Part 2, which has just started, begins patient randomization, comparing the efficacy of liposomal irinotecan to topotecan, the current standard of care. Key endpoints for Part 2 are progression-free survival and overall survival.
Data from Part 1 were presented at the WCLC. The analysis included 30 patients with a median age of 60 years (range, 48-73). In the dose-finding phase, patients received liposomal irinotecan at 70 mg/m2
or 85 mg/m2
every 2 weeks. However, after 5 patients receiving 85 mg/m2
experienced a dose-limiting toxicity, the dose level was considered not tolerable. During this phase, 12 patients received the 70 mg/m2
dose, which was deemed to be tolerable. Thus an additional 13 patients were treated at 70 mg/m2
, for a total of 25 patients.
Among the 25-patient group who received the 70 mg/m2
dose, 40% (n = 10) were male, the median age was 59 years, and 88% had an ECOG performance status of 1. The median time since most recent disease progression was 3.2 weeks, 2 patients had locally advanced disease, and 23 patients had metastatic disease. Twelve patients had completed the study, 7 remained on study, and 6 patients had died. Two patient deaths resulted from an adverse event related to the study drug.
Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 40% (n = 10) of patients. The most common grade 3 gastrointestinal TEAE was diarrhea (n = 5). Grade ≥3 hematologic TEAEs included neutropenia (n = 4), anemia (n = 2), and thrombocytopenia (n = 2). There was also one case of grade ≥3 fatigue.
Liposomal irinotecan is a nanoliposomal encapsulation of irinotecan, allowing for the drug to stay in circulation for a longer duration compared with standard irinotecan. Additionally, this mechanism allows for higher drug uptake within tumor cells and conversion of irinotecan to its active form, SN38.
The FDA approved liposomal irinotecan in October 2015 for use in combination with 5-fluorouracil (5-FU) and leucovorin as a treatment for patients with metastatic pancreatic cancer following prior administration of a gemcitabine-based regimen.
“Onivyde has been proven to help many metastatic pancreatic cancer patients whose disease has progressed following gemcitabine-based therapy to live longer,” Yan Moore, MD, senior vice president, head of Oncology Therapeutic Area, Ipsen, which develops liposomal irinotecan along with Servier, said in a press release. “By applying this research to other hard-to-treat-cancers, like small cell lung cancer, we aim to evaluate the potential benefit investigational Onivyde may bring to patients who otherwise would have limited treatment options.”
<<< 2019 World Conference on Lung Cancer
- Ipsen and Servier announce initial phase II/III clinical data evaluating investigational liposomal irinotecan (Onivyde®) as a second-line treatment for small cell lung cancer (SCLC) at the IASLC 2019 world conference on lung cancer. Ipsen. Published September 8, 2019. Accessed September 9, 2019. https://bit.ly/2lPeuHL.
- Paz-Ares L, Spigel D, Chen Y, et al. Initial efficacy and safety results of irinotecan liposome injection (NAL-IRI) in patients with small cell lung cancer. Presented at: IASLC 20th World Conference on Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract OA03.03.