Lurbinectedin as monotherapy was found to elicit responses in patients with relapsed small cell lung cancer (SCLC), meeting the primary endpoint of a phase II trial by both investigator review and an independent review committee.1
The updated phase II findings are slated to be presented at an upcoming medical meeting, announced PharmaMar, the manufacturer of the investigational RNA polymerase II inhibitor.
In the multicenter, single-arm, phase II basket study (NCT02454972), investigators evaluated the safety and efficacy of lurbinectedin in 345 patients with the following advanced solid tumors: SCLC, head and neck cancer, neuroendocrine tumors, biliary tract cancer, endometrial cancer, BRCA1/2
-mutant metastatic breast cancer, carcinoma of unknown primary site, germ cell tumors, and Ewing’s family of tumors.
Specifically, the trial included 105 patients with SCLC from 38 centers and in 9 countries. Patients with SCLC who were eligible for enrollment had 1 prior line of chemotherapy, an ECOG performance status ≤2, and adequate major organ function. Prior treatment with lurbinectedin or trabectedin (Yondelis), prior or concurrent malignant disease, known CNS involvement, and relevant diseases or clinical situations that increase the patient’s risk were exclusion criteria.
The primary endpoint was ORR; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
Preliminary phase II data were presented at the 2018 ASCO Annual Meeting. In the SCLC cohort, patients did not have CNS metastases and received 1 prior line of chemotherapy. If one complete response was reported, it was decided that the recruitment would be increased to 100 patients. Lurbinectedin was administered at 3.2 mg/m2
as a 1-hour intravenous (IV) infusion every 3 weeks.
Of all 68 patients enrolled, the median age was 60.5 years (range, 40-83). There were more males (n = 43) than females (n = 25), and most patients had an ECOG performance score of 1 (n = 43).
Results showed that, of 61 evaluable patients treated with lurbinectedin, the ORR was 39.3% (95% CI, 27.1%-52.7%).2
The clinical benefit rate was 50.8% (95% CI, 37.7%-63.9%), and the disease control rate (DCR) was 73.8% (60.9%-94.2%). Additionally, the median DOR was 6.2 months, the median PFS was 4.1 months, and the median OS was 11.8 months.
When stratified by chemotherapy-free interval (CTFI), patients with a CTFI <90 days (n = 27) had an ORR of 33.3% (95% CI, 16.5%-54%) and those with a CTFI ≥90 days (n = 34) had an ORR of 44.1% (95% CI, 27.2-62.1%). In those with a CTFI <90 days, the clinical benefit rate was 44.4% (95% CI 25.5%-64.7%), the DCR was 63% (42.4%-80.6%), the median DOR was 4.1 months, the median PFS was 3.4 months, and the median OS was 8.1 months.
For those with a CTFI ≥90 days, the clinical benefit rate was 55.9% (95% CI, 37.9%-72.8%), the DCR was 82.4% (95% CI, 65.5%-93.2%), the median DOR was 6.2 months, median PFS was 4.2 months, and the median OS was 15.8 months.
Regarding safety, myelosuppression was the most commonly observed adverse event. Thirty-nine percent of patients experienced grade 3/4 neutropenia, and febrile neutropenia was reported in 9% of patients. Dose delays and reductions due to neutropenia occurred in 8 and 10 patients, respectively. Granulocyte-colony stimulating factor was administered in 11 patients.
The phase III ATLANTIS study (NCT02566993), which is evaluating the combination of lurbinectedin with doxorubicin as a second-line treatment for patients with SCLC, completed patient recruitment in July 2018; results are anticipated.
The FDA granted lurbinectedin an orphan drug designation in August 2018, which was followed by the European Medicines Agency decision to also grant the agent orphan drug designation in January 2019, both in SCLC.
- PharmaMar announces positive results in its lurbinectedin monotherapy trial for small cell lung cancer. PharmaMar. Published March 25, 2019. https://bit.ly/2HSnMvC. Accessed March 25, 2019.
- Trigo JM, Leary A, Besse B, et al. Efficacy and safety of lurbinectedin (PM1183, ZEPSYRE) in small cell lung cancer (SCLC): results from a phase 2 study. J Clin Oncol. 2018;36 (suppl; abstr 8570). doi: 10.1200/JCO.2018.36.15_suppl.8570.