Amrubicin and carboplatin with pegfilgrastim in patients with extensive-stage small-cell lung cancer (ES-SCLC): A phase II study of the Sarah Cannon Research Institute (SCRI).
7100 Background: Amrubicin is a novel anthracycline associated with high objective response rates (ORR) in patients (pts) with relapsed SCLC. Amrubicin improved the ORR and progression-free survival (PFS) in relapsed SCLC vs. topotecan, but not overall survival (OS) in a phase III study. Amrubicin with cisplatin/carboplatin for elderly Japanese pts was safe and active. We conducted a multicenter phase II study evaluating amrubicin and carboplatin in newly diagnosed ES-SCLC. Methods: Eligible pts had untreated ES-SCLC, measurable/evaluable disease (RECIST v. 1.1) and an ECOG PS <2. Pts received 4 cycles of amrubicin 30 mg/m2 on days 1-3 and carboplatin AUC=5 both IV day 1 every 21 days with restaging every 6 weeks. Pegfilgrastim 6 mg sq was administered on day 4 of each cycle. The primary endpoint was 1-year OS. Secondary endpoints included ORR, PFS, OS, and toxicity. Results: 78 pts were enrolled from 3/2010 to 7/2011. Baseline characteristics included: median age 65 yrs (range 45-84); 56% female. 64% completed 4 cycles of treatment. Eleven (14%) pts showed complete responses and 47 (60%) pts partial responses, for an ORR of 74% (95% confidence interval 65%-82%). Twelve (15%) pts had stable disease. Median PFS and OS were 5.3 and 9.5 months, respectively. The 1-year OS was 36%. Grade 3/4 myelosuppression was the most common toxicity (thrombocytopenia 44%, neutropenia 34%, febrile neutropenia 12%, anemia 26%), but was manageable. Severe non-hematologic toxicities (>5%) included hypokalemia 17%, fatigue 13%, dehydration 10%, hyponatremia 10%, pneumonia 9%, and nausea/vomiting 8%. 1 pt died from sepsis and another from aspiration pneumonia. Conclusions: First-line ES-SCLC treatment with amrubicin and carboplatin induced several complete responses and is considered highly active. Myelosuppression was managed effectively with growth factor support. These results are comparable to historical data with platinum-doublet chemotherapy. A larger randomized study would be required to best assess this regimen’s impact on survival.