Small cell lung cancer: © Констянтин Батыльчук- stock.adobe.com
An international study evaluating lurbinectedin (Zepzelca) in second-, third-, and later-lines of therapy in patients with extensive stage small cell lung cancer (ES-SCLC) in the Netherlands and Italy demonstrated an objective response rate (ORR) of 23.1%, a disease control rate (DCR) of 45.5%, a median progression-free survival (PFS) of 2.2 months (95% CI, 1.6–2.8) and a median overall survival (OS) of 5.4 months (95% CI, 4.5–6.3). In particular, patients with a chemotherapy-free interval (CFI) of 90 days or more showed a longer PFS (3.1 vs 1.8 months; HR, 0.46; 95% CI, 0.30–0.71; P <.0001) and OS (6.8 vs 4.5 months; HR, 0.56; 95% CI, 0.37–0.86; P =.006).
The prospective study enrolled 238 patients in the Netherlands (n = 204) and Italy (n = 34) who received 3.2 mg/m2 of lurbinectedin every 3 weeks. The primary end points were ORR, DCR, PFS, OS, and safety. The secondary end points and exploratory objectives were clinical-pathological characteristics, treatment management, and antitumor activity according to chemotherapy sensitive (CFI ≥ 90 days) and resistant (CFI < 90 days) disease.
Across both cohorts, the median age was 65 years (range, 39-87) and there were more females in the Netherlands cohort (54.4%) compared with the Italian cohort (32.4%). Most patients had a diagnosis of SCLC: all (94.5%), the Netherlands (94.1%), and Italy (97.1%).
Regarding smoking status, 6.3% of patients were never smokers, 6.9% of patients in the Netherlands were never smokers, and 2.9% of patients in Italy were never smokers. Current smokers numbered 28.6%, 26.5%, and 41.2%, respectively.
For previous treatments, the median previous line of treatment was 2 (range, 1–7); 2 (range, 1–7); and 1 (range, 1–4), respectively. Overall, the majority of patients had 2 previous lines of treatment (40.7%) and in the Netherlands (42.6%) but in the Italian cohort, the majority of patients had 1 previous line of treatment (52.9%).
Overall, at lurbinectedin start, metastasis was observed in the liver (45.8%), bone (32.%), brain (22.3%), and others (96.2%). The Netherlands cohort and Italian cohort had similar patterns.
Lurbinectedin was administered as second line treatment in 87 (37 %), as third line in 107 (45 %) and as later lines in 44 (18 %) patients.
After a median follow-up of 5.53 months (IQR, 4.61–11.71 months), treatment discontinuation occurred in 98% of patients, mainly because of disease progression (PD; 89%). The ORR was 23.1% (95 %CI, 17.8%–28.4%) with a notable difference between the Dutch cohort (24.5%, 95%CI, 18.6%–30.4%) and the Italian cohort (14.7%, 95% CI, 2.7%–23.9%). Similarly, the DCR was 45.4% (95% CI, 39.1%–51.7%) in the entire population enrolled, 48.0% (95% CI, 41.2%–54.9%) in the Dutch patients, and 29% (95% CI, 15.1%–47.5%) in the Italian patients.
Overall, the median duration of response (mDOR) was 2.8 months (95% CI, 2.0–3.5), the mPFS was 2.2 months (95% CI, 1.6–2.8) and the mOS was 5.4 months (95%CI, 4.5–6.3). The 6-month PFS and OS rates were respectively 12.2% (95% CI, 8.3–17.0) and 42.4% (95% CI, 36.1–49.0).
Regarding safety, lurbinectedin was well tolerated and treatment-related adverse events (TRAEs) of any grade were 92% for all patients and 29% in any patients experiencing at least 1 grade 3 or 4 toxicity.
The most common AE was fatigue (46%), followed by anemia (38%), neutropenia (35%), increased gamma-glutamyl transferase (GGT) levels (24%), and increased aspartate transferase or alanine aminotransferase levels (22%). The most frequently reported grade 3 or 4 AE was neutropenia (22%).
Daniela Scattolin and colleagues noted that a higher proportion of Italian patients previously treated with chemoimmunotherapy (65%) compared with the Netherlands (12%). They wrote that, “This disparity reflects the differing treatment guidelines for ES-SCLC, where chemoimmunotherapy is currently not reimbursed in the Netherlands.” This disparity was not statistically significant, however, as no differences were observed in PFS and OS between patients who had or not received prior chemoimmunotherapy.
Although this is one of the largest multicentric cohort studies across 2 European countries, the investigators noted a number of limitations. These include its retrospective design, the small number of patients and centers involved, and the imbalance in cohort size between the 2 countries. There was also heterogeneity in baseline patient characteristics, treatment management strategies, and tumor assessment protocols.