Australian experience of novel SCLC drug ‘reassuring’

Lung cancer

By Siobhan Calafiore

29 Feb 2024

Australia’s experience of lurbinectedin for patients with advanced refractory small cell lung cancer (SCLC) is similar to that reported in clinical trials, providing reassurances of real-world efficacy and toxicities, researchers say.

The synthetic alkaloid is a selective inhibitor of oncogenic transcription, which received provisional approval for use in Australia in 2021 under the brand name Zepzelca.

To assess its use in Australia, a team at Peter Mac Cancer Centre, Melbourne, analysed real-world data from 46 patients with small cell lung cancer (SCLC) initiating lurbinectedin monotherapy (3.2 mg/m2 three-weekly) across seven sites as part of an early access program in Australia between May 2020 and December 2021.

All patients (median age 67, 57% female) had extensive stage disease by the time of lurbinectedin initiation, most of which involved two or more metastatic sites of disease (72%); mostly bone (48%), liver (46%), lung (46%) and brain (39%).

The novel oncogenic transcription inhibitor was given as a second- (83%) or subsequent- (17%) line therapy, mostly with prior chemoimmunotherapy (87%), said the study authors.

All patients received first-line platinum doublet therapy (96% carboplatin), with the majority in combination with ICI (atezolizumab (n = 35); durvalumab (n = 2)).

Only two individuals were alive at data cutoff and both had discontinued lurbinectedin, one because of toxicity and the other because of progression.

The median duration of therapy was 64 days and half of the cohort received three or fewer cycles of lurbinectedin.

Writing in the Internal Medicine Journal [link here], the researchers said dose modifications (17%) and interruptions/delays (24%) were common, while there were also high-grade toxicities (28%) and hospitalisations (54%) during treatment.

Almost half of the hospitalisations were related to lurbinectedin.

The overall response rate was 33% and the disease control rate was 50%. For second and subsequent lines, the overall response rate was 26% and 56%, respectively.

Among other findings, the median progression-free survival was 2.5 months and the median overall survival was 4.5 months from the first lurbinectedin dose.

Overall survival was 44% at six months and 15% at 12 months.

From SCLC diagnosis, the median overall survival was 12.9 months and the overall survival rate was 94% at six months, 63% at one year and 22% at two years.

The researchers noted that patients with a longer chemotherapy-free interval prior to lurbinectedin had longer progression-free survival and overall survival.

“In the current study, the median overall survival in the ICI-exposed cohort was 4.4 months compared to 12.9 months in the small group (n = 6) with no prior ICI exposure,” they wrote.

“Notably, all six individuals not exposed to ICI appeared to have chemotherapy- sensitive disease demonstrated by chemotherapy-free interval >90 days and median chemotherapy-free interval more than double that of the cohort median (median 251 days vs 89 days).

“Confirmation that chemotherapy-free interval rather than ICI exposure likely explains survival differences would be reassuring if included in the forthcoming full publication of the US Flatiron data.”

They said that their study was one of few real-world reports and the first outside the United States and Europe. It showed that the real-world national experience of lurbinectedin post-platinum chemotherapy and immunotherapy for individuals with SCLC was similar to that previously reported in clinical trials.

Specialised Therapeutics provided lurbinectedin and contributed funding to support the study but had no input in the interpretation of results or content. Some authors declared receiving funding from pharmaceutical companies.

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