A new drug application (NDA) has been registered for expedited approval with the FDA for lurbinectedin in sufferers with small-cell lung cancer (SCLC) who have improved after prior platinum-containing treatment, according to the company, PharmaMar. The filing was based on outcomes from a phase II basket trial, performed at the 2019 ASCO Annual Meeting.
In the trial (NCT02454972), single-agent lurbinectedin confirmed an overall response rate (ORR) of 35.2% in the second-line background. The ORR consisted of all partial acknowledgments, which happened in 37 of 105 patients. An additional 35 sufferers had a stable illness, for a condition control rate of 68.6% (95% CI, 58.8%-77.3%). Overall, 65% of patients had a decrease in tumor size, and acknowledgments occurred in 5 of 8 patients who had failed prior immunotherapy. Twenty-eight patients (26.7%) had a progressive illness, and five patients were not evaluable.
The Report Done
Researchers reported that the median duration of the answer was 5.3 months (95% CI, 4.1-6.4). They noted that the response rate was higher in patients with a painful illness, characterized as those with a chemotherapy-free interval (CTFI) ≥ 90 days. Among those sufferers, the ORR was 45% compared with 22.2% in patients with resistant disease (CTFI <90 days).
In the multicenter, single-arm study, researchers assessed the safety and effectiveness of lurbinectedin in sufferers across advanced solid tumors, including SCLC, head and neck cancer, neuroendocrine tumors, biliary tract cancer, endometrial cancer, BRCA1/2-mutant metastatic breast cancer, carcinoma of private primary site, germ cell tumors, and Ewing’s family of tumors.
The 105 sufferers in the SCLC cohort were recorded between October 2015 and October 2018. The median patient age was 60 years (range, 40-83), and 35.2% of sufferers were aged ≥65 years. The ECOG performance status was 0 for 36.2% of patients, 1 for 56.2% of patients, and 2 for 7.6% of patients.
The median number of prior treatments was 1 (range, 1-2). Regarding the reply to prior platinum-based therapy, 8.6% of patients had a complete response, and 66.7% of patients had a partial answer. Fifty-seven percent (n = 60) of patients had sore illness and 43% (n = 45) of patients had immune disease.
Overall, the median progression-free survival (PFS) was 3.9 months (95% CI, 2.6-4.6), and the 6-month PFS rate was 33.6% (95% CI, 24.0-43.1). In the sensitive subgroup, the median PFS was 4.6 months (95% CI, 3.0-6.5), and the 6-month PFS rate was 44.6% (95% CI, 31.2%-57.9%). In the resistant population, the median PFS was 2.6 months (95% CI, 1.3-3.9), and the 6-month PFS rate was 18.8 months (95% CI, 6.8-30.9).
The Accelerated Support
At a median follow-up of 17.1 months, the median OS was 9.3 months (95% CI, 6.3-11.8), and the 12-month OS rate was 34.2% (95% CI, 23.2-45.1). The median OS was 11.9 months in receptive sufferers versus 5.0 months in immune patients.
The accelerated support allows for the submission of an NDA for evaluation based on outcomes of phase II drug trials for the therapy of diseases with unmet needs. Notably, the procedure for SCLC has not changed considerably in more than two decades, with the approval of topotecan in 1996. Historically, acknowledgment rates with that agent in this set range from 5% to 24%, with a median overall survival of 6 to 8 months.
“It is excellent to see some different healing options arriving for small cell lung cancer patients, who represent a major unmet medical necessity,” Charles Rudin, MD, chief of the thoracic oncology service and co-director of the Druckenmiller Center for Lung Cancer Research at Memorial Sloan Kettering Cancer Center in New York, NY, said in a statement.
Adverse events (AEs) across all grades happened in 84.8% of patients, with 34.3% of patients experiencing a grade ≥3 AE. Serious AEs were observed in 10.5% of patients. AE-related discontinuations, dose delays, and dose reductions occurred in 1.9%, 22.1%, and 26.3% of patients, respectively. There were no AE-related deaths.
The most common grade 1/2 AEs included fatigue (51.4%), nausea (32.4%), decreased appetite (21.0%), vomiting (18.1%), diarrhea (12.4%), constipation (9.5%), and neutropenia (5.7%). Grade 3/4 AEs included neutropenia (22.9%), anemia (6.7%), fatigue (6.7%), thrombocytopenia (4.8%), febrile neutropenia (4.8%), pneumonia (1.9%), increase ALT level (1.9%), skin ulcer (1.0%), and diarrhea (1.0%).