2 research outputs found
A phase III, randomized, double-blind, multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer
Objectives: Efficacy, safety, pharmacokinetics (PK), and immunogenicity of the biosimilar candidate SB8 was
compared to its reference product bevacizumab (BEV) in patients with metastatic or recurrent nonsquamous
nonāsmall cell lung cancer.
Methods: Patients were randomized (1:1) in a phase III, double-blind study to receive intravenous SB8 or BEV
15 mg/kg with paclitaxel/carboplatin every 3 weeks for 24 weeks, followed by SB8 or BEV maintenance
monotherapy. The primary endpoint was best overall response rate (ORR) by 24 weeks. Secondary endpoints
included survival outcomes, safety, PK, and immunogenicity.
Results: 763 patients (SB8, n = 379; BEV, n = 384) were randomized; baseline characteristics were well balanced. Best ORR in the FAS was 47.6% and 42.8%, and best ORR in the PPS was 50.1% and 44.8% for SB8 and
BEV, respectively. The risk ratio of best ORR was 1.11 (90% CI, 0.975ā1.269), and the risk difference in best
ORR was 5.3% (95% CI, ā2.2%ā12.9%). Median survival outcomes were comparable between SB8 and BEV:
progression-free survival was 8.50 vs 7.90 months, respectively (HR [95% CI], 0.99 [0.83ā1.18]; p = 0.9338);
overall survival was 14.90 vs 15.80 months, respectively (HR [95% CI], 1.03 [0.83ā1.28]; p = 0.7713); and
duration of response was 7.70 vs 7.00 months, respectively (HR [95% CI], 1.05 [0.81ā1.37]; p = 0.6928).
Severity and incidence of treatment-emergent adverse events, PK, and immunogenicity were comparable between SB8 and BEV.
Conclusion: This study demonstrated equivalence between SB8 and BEV in terms of best ORR risk ratio, with
comparable safety, PK, and immunogenicity
Durvalumab, with or without tremelimumab, plus platinumāetoposide versus platinumāetoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN):updated results from a randomised, controlled, open-label, phase 3 trial
Background: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinumāetoposide) showed a significant improvement in overall survival versus platinumāetoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinumāetoposide versus platinumāetoposide alone. Methods: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinumāetoposide, durvalumab plus platinumāetoposide, or platinumāetoposide alone. In all groups, patients received etoposide 80ā100 mg/m2 on days 1ā3 of each cycle with investigator's choice of either carboplatin area under the curve 5ā6 mg/mL/min or cisplatin 75ā80 mg/m2 on day 1 of each cycle. Patients in the platinumāetoposide group received up to six cycles of platinumāetoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinumāetoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinumāetoposide versus platinumāetoposide and for durvalumab plus tremelimumab plus platinumāetoposide versus platinumāetoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. Findings: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinumāetoposide, 268 to durvalumab plus platinumāetoposide, and 269 to platinumāetoposide). As of Jan 27, 2020, the median follow-up was 25Ā·1 months (IQR 22Ā·3ā27Ā·9). Durvalumab plus tremelimumab plus platinumāetoposide was not associated with a significant improvement in overall survival versus platinumāetoposide (hazard ratio [HR] 0Ā·82 [95% CI 0Ā·68ā1Ā·00]; p=0Ā·045); median overall survival was 10Ā·4 months (95% CI 9Ā·6ā12Ā·0) versus 10Ā·5 months (9Ā·3ā11Ā·2). Durvalumab plus platinumāetoposide showed sustained improvement in overall survival versus platinumāetoposide (HR 0Ā·75 [95% CI 0Ā·62ā0Ā·91]; nominal p=0Ā·0032); median overall survival was 12Ā·9 months (95% CI 11Ā·3ā14Ā·7) versus 10Ā·5 months (9Ā·3ā11Ā·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinumāetoposide group, 64 [24%] of 265 patients in the durvalumab plus platinumāetoposide group, and 88 [33%] of 266 patients in the platinumāetoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinumāetoposide group, 85 (32%) in the durvalumab plus platinumāetoposide group, and 97 (36%) in the platinumāetoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinumāetoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinumāetoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinumāetoposide group (pancytopenia and thrombocytopenia [n=1 each]). Interpretation: First-line durvalumab plus platinumāetoposide showed sustained overall survival improvement versus platinumāetoposide but the addition of tremelimumab to durvalumab plus platinumāetoposide did not significantly improve outcomes versus platinumāetoposide. These results support the use of durvalumab plus platinumāetoposide as a new standard of care for the first-line treatment of ES-SCLC. Funding: AstraZeneca.</p