After Platinum-Based Therapy, Liposomal Irinotecan Appears Effective, Safe for Second-Line SCLC


Liposomal irinotecan as second-line therapy for SCLC is feasible, safe after frontline platinum therapy failure.

Frontline treatment failure of platinum-based therapy may be followed by liposomal irinotecan in SCLC according to data from the first phase of the RESILIENT trial (NCT03088813) presented at the 2020 World Conference on Lung Cancer showing promising antitumor activity and safety with this strategy.

The study authors initiated the 2-part phase 2/3 open-label, single-arm study to assess liposomal irinotecan in patients with SCLC whose disease progressed after receiving platinum-based chemotherapy in the frontline. Treatment options in the second-line setting remain limited but analyzing long-term follow-up data demonstrated that both exploratory doses of liposomal irinotecan were effective and tolerable in patients with SCLC. Patients who were older than 18, had an ECOG performance score of 0 or 1, and had previously progressed on platinum-based treatments were eligible for the study. RESILIENT was designed around 2 doses of liposomal irinotecan to see which was ultimately more effective, either an 85 mg/m2 or 70 mg/m2 dose administered every 2 weeks.

In the first part of the study, 30 patients (median age, 61.5 years) received the study drug. Women accounted for more than half (56.7%) of the trial population. Four of the 5 patients from the 85 mg/m2 cohort had dose-limiting toxicities such as diarrhea and abnormal liver function and were considered to not have tolerated the dose.

The remaining patients (n = 25) were immediately enrolled onto the 70 mg/m2 dose arm. One patient achieved a complete response, 10 patients achieved a partial response, 7 had stable disease, 5 developed progressive disease, and 2 patients were considered not evaluable. The median duration of response in the 70 mg/m2 cohort was 2.99 months and median progression-free survival was 3.98 months (95% CI; 1.45–4.24). Median overall survival reached 8.08 months (95% CI; 5.16–9.82) in this cohort.

Treatment-related adverse effects were consistent with previous safety findings in liposomal irinotecan. However, all patients from both treatment arms have discontinued treatment. Forty percent of the expansion arm experienced one or more grade 3 or higher treatment-related treatment-emergent adverse event (TEAE). The most common grade 3 or higher treatment-related TEAEs were diarrhea (20%), neutropenia (16%), anemia, thrombocytopenia, asthenia, and abdominal sepsis (each 8% of the total patient population).

“Liposomal irinotecan raised no new safety signals in patients with small cell lung cancer and the anti-tumor activity observed was promising, warranting further study,” study author Luis G Paz-Ares, MD, PhD, of the Hospital Universitario 12 De Octubre in Madrid, said in a prerecorded presentation of the data.


Paz-Ares L, Spigel D, Chen Y, et al. RESILIENT part 1: a phase II dose-exploration and dose expansion study of second-line liposomal irinotecan monotherapy in adults with small cell lung cancer. Presented at: 2020 World Conference on Lung Cancer Singapore; January 28-31, 2021; Virtual. Abstract FP10.04

Related Videos
Common adverse effects following treatment with lenvatinib plus pembrolizumab in the phase 3 CLEAR study include diarrhea, hypertension, and fatigue, according to Thomas E. Hutson, DO, PharmD, FACP.
Lenvatinib in combination with pembrolizumab appears to raise no new safety signals in patients with advanced clear cell renal cell carcinoma after 4 years of follow-up in the phase 3 CLEAR study.
According to Thomas E. Hutson, DO, PharmD, FACP, 4-year follow-up data from the phase 3 CLEAR study confirm the maintained benefits of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma.
Findings from the phase 3 MIRASOL trial support mirvetuximab soravtansine as a standard treatment option for platinum-resistant ovarian cancer, according to Ritu Salani, MD.
Rana R. McKay, MD discusses presentations of interest that were presented at the 2023 Kidney Cancer Research Summit, including a discussion on how PET imaging may identify which patients with renal cell carcinoma may respond to immunotherapy.
A better understanding of tumor biology may be necessary for identifying novel non-immunotherapy–based therapeutic strategies for patients with renal cell carcinoma, according to Rana R. McKay, MD.
Probiotics and other agents targeting fatty acid oxidation are also under evaluation as treatment options for patients with renal cell carcinoma, according to Rana R. McKay, MD.
Other angiogenic agents are also under investigation in renal cell carcinoma, according to Rana McKay, MD, who indicates it will be interesting to see how they compare with belzutifan.
Trastuzumab deruxtecan appears to elicit ‘impressive’ responses among patients with HER2-positive gynecologic cancers regardless of immunohistochemistry in the phase 2 DESTINY-PanTumor02 trial.
Ritu Salani, MD, highlights the possible benefit of a novel targeted therapy and autologous tumor vaccine in patients with platinum-resistant ovarian cancer, and in the maintenance setting after treatment for platinum-sensitive disease.