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Correction: Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F®) in couples undergoing assisted reproductive technology treatment: a systematic review and meta-analysis This was based on the mean ± standard deviation (SD) number of oocytes retrieved, which was reported by Hu et al. in Table 2 of their publication (14.9 ± 0.5 for Follitrope [ I n i = 336] and 12.8 ± 0.9 for GONAL-f® [ I n i = 110]) [[2]]. When comparing the SD values reported in Table 2 [[2]] with those from the other four RCTs included our meta-analysis (NCT01121666, NCT01687712, ISRCTN74772901 and NCT03088137) [[1]], the values are unusually small and inconsistent with the range of SDs reported for the other four RCTs. [Extracted from the article]

Bintrafusp alfa, a first‐in‐class bifunctional fusion protein composed of the extracellular domain of TGF‐βRII (a TGF‐β "trap") fused to a human IgG1 mAb blocking PD‐L1, is being evaluated for efficacy and safety in solid tumor indications as monotherapy and in combination with small‐molecule drugs. We evaluated the perpetrator drug–drug interaction (DDI) potential of bintrafusp alfa via cytochrome P4503A4 (CYP3A4) enzyme modulation, which is responsible for the metabolism of a majority of drugs. The holistic approach included (1) evaluation of longitudinal profiles of cytokines implicated in CYP3A4 modulation and serum 4β‐hydroxycholesterol, an endogenous marker of CYP3A4 activity, in a phase I clinical study, and (2) transcriptomics analysis of the CYP3A4 mRNA levels vs the TGFB gene expression signature in normal hepatic tissues. Bintrafusp alfa was confirmed not to cause relevant proinflammatory cytokine modulation or alterations in 4β‐hydroxycholesterol serum concentrations in phase I studies. Transcriptomics analyses revealed no meaningful correlations between TGFB gene expression and CYP3A4 mRNA expression, supporting the conclusion that the risk of CYP3A4 enzyme modulation due to TGF‐β neutralization by bintrafusp alfa is low. Thus, bintrafusp alfa is not expected to have DDI potential as a perpetrator with co‐administered drugs metabolized by CYP3A4; this information is relevant to clinical evaluations of bintrafusp alfa in combination settings. [ABSTRACT FROM AUTHOR]

Objectives Unresectable stage III NSCLC (non–small cell lung cancer) confers a poor prognosis and interest is growing in the use of immunotherapy to improve outcomes for patients with this disease. We investigated the safety and efficacy of maintenance tecemotide, a mucin 1 (MUC1)-specific agent that induces T-cell responses to MUC1, versus placebo in Japanese patients with stage III unresectable NSCLC and no disease progression after primary chemoradiotherapy. Materials and methods Patients aged ≥20 years with unresectable stage III NSCLC, stable disease or clinical response after primary chemoradiotherapy and performance status ≤1, were recruited across 25 centers in Japan. Patients were randomized 2:1 to tecemotide (930 μg as lipopeptide) or placebo subcutaneously once weekly for 8 weeks, then every 6 weeks until disease progression or treatment withdrawal. Cyclophosphamide 300 mg/m 2 (maximum dose 600 mg) was given intravenously 3 days before the first dose of tecemotide. The primary endpoint was overall survival (OS). Secondary endpoints were progression–free survival, time to progression, time to treatment failure and safety. Results The intent–to–treat population comprised 172 patients; 114 received tecemotide and 58 placebo. Baseline characteristics were comparable between treatment arms. Most patients (94%) received primary concurrent chemoradiotherapy. There was no apparent trend toward increased OS time with tecemotide over placebo (median 32.4 versus 32.2 months, hazard ratio 0.95, 95% confidence interval 0.61–1.48; P = 0.83). No improvements in secondary efficacy endpoints were observed. The frequency of treatment–related adverse events was similar, and serious adverse event rates were the same in both arms. There were no new safety signals. Conclusions These results do not support those from a randomized phase III study (START) of improved OS with tecemotide in the subgroup of patients treated with primary concurrent chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Summary: Background: Effective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific cancer immunotherapy tecemotide improves survival in patients with stage III unresectable non-small-cell lung cancer when given as maintenance therapy after chemoradiation. Methods: The phase 3 START trial was an international, randomised, double-blind trial that recruited patients with unresectable stage III non-small-cell lung cancer who had completed chemoradiotherapy within the 4–12 week window before randomisation and received confirmation of stable disease or objective response. Patients were stratified by stage (IIIA vs IIIB), response to chemoradiotherapy (stable disease vs objective response), delivery of chemoradiotherapy (concurrent vs sequential), and region using block randomisation, and were randomly assigned (2:1, double-blind) by a central interactive voice randomisation system to either tecemotide or placebo. Injections of tecemotide (806 μg lipopeptide) or placebo were given every week for 8 weeks, and then every 6 weeks until disease progression or withdrawal. Cyclophosphamide 300 mg/m2 (before tecemotide) or saline (before placebo) was given once before the first study drug administration. The primary endpoint was overall survival in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00409188. Findings: From Feb 22, 2007, to Nov 15, 2011, 1513 patients were randomly assigned (1006 to tecemotide and 507 to placebo). 274 patients were excluded from the primary analysis population as a result of a clinical hold, resulting in analysis of 829 patients in the tecemotide group and 410 in the placebo group in the modified intention-to-treat population. Median overall survival was 25·6 months (95% CI 22·5–29·2) with tecemotide versus 22·3 months (19·6–25·5) with placebo (adjusted HR 0·88, 0·75–1·03; p=0·123). In the patients who received previous concurrent chemoradiotherapy, median overall survival for the 538 (65%) of 829 patients assigned to tecemotide was 30·8 months (95% CI 25·6–36·8) compared with 20·6 months (17·4–23·9) for the 268 (65%) of 410 patients assigned to placebo (adjusted HR 0·78, 0·64–0·95; p=0·016). In patients who received previous sequential chemoradiotherapy, overall survival did not differ between the 291 (35%) patients in the tecemotide group and the 142 (35%) patients in the placebo group (19·4 months [95% CI 17·6–23·1] vs 24·6 months [18·8–33·0], respectively; adjusted HR 1·12, 0·87–1·44; p=0·38). Grade 3–4 adverse events seen with a greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024 patients in the tecemotide group vs 21 [4%] of 477 patients in the placebo group), metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia (23 [2%] vs 12 [3%]). Serious adverse events with a greater than 2% frequency with tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ between groups. Interpretation: We found no significant difference in overall survival with the administration of tecemotide after chemoradiotherapy compared with placebo for all patients with unresectable stage III non-small-cell lung cancer. However, tecemotide might have a role for patients who initially receive concurrent chemoradiotherapy, and further study in this population is warranted. Funding: Merck KGaA (Darmstadt, Germany). [ABSTRACT FROM AUTHOR]