Cost-effectiveness analysis of neoadjuvant pertuzumab and trastuzumab therapy for locally advanced, inflammatory, or early HER2-positive breast cancer in Canada.

OBJECTIVE: The NeoSphere trial demonstrated that the addition of pertuzumab to trastuzumab and docetaxel for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early breast cancer (eBC) resulted in a significant improvement in pathological complete response (pCR). Furthermore, the TRYPHAENA trial supported the benefit of neoadjuvant dual anti-HER2 therapy. Survival data from these trials is not yet available; however, other studies have demonstrated a correlation between pCR and improved event-free survival (EFS) and overall survival (OS) in this patient population. This study represents the first Canadian cost-effectiveness analysis of pertuzumab in the neoadjuvant treatment of HER2-positive eBC. METHODS: A cost-utility analysis (CUA) was conducted using a three health state Markov model ('event-free', 'relapsed', and 'dead'). Two separate analyses were conducted; the first considering total pCR (ypT0/is ypN0) data from NeoSphere, and the second from TRYPHAENA. Published EFS and OS data partitioned for patients achieving/not achieving pCR were used in combination with the percentage achieving pCR in the pertuzumab trials to estimate survival. This CUA included published utility values and direct medical costs including drugs, treatment administration, management of adverse events, supportive care, and subsequent therapy. To address uncertainty, a probabilistic sensitivity analysis (PSA) and alternative scenarios were explored. RESULTS: Both analyses suggested that the addition of pertuzumab resulted in increased life-years and quality-adjusted life-years (QALYs). The incremental cost per QALY ranged from $25,388 (CAD; NeoSphere analysis) to $46,196 (TRYPHAENA analysis). Sensitivity analyses further support the use of pertuzumab, with cost-effectiveness ratios ranging from $9230-$64,421. At a threshold of $100,000, the addition of pertuzumab was cost-effective in nearly all scenarios (93% NeoSphere; 79% TRYPHAENA). CONCLUSION: Given the improvement in clinical efficacy and a favorable cost per QALY, the addition of pertuzumab in the neoadjuvant setting represents an attractive treatment option for HER2-positive eBC patients.

Brassica genomics: a complement to, and early beneficiary of, the Arabidopsis sequence.

Those studying the genus Brassica will be among the early beneficiaries of the now-completed Arabidopsis sequence. The remarkable morphological diversity of Brassica species and their relatives offers valuable opportunities to advance our knowledge of plant growth and development, and our understanding of rapid phenotypic evolution.

Assessment of DNA pooling strategies for mapping of QTLs.

The synthesis of "DNA pools" from segregating populations is an efficient strategy for identifying DNA markers closely linked to genes or genomic regions of interest. To-date, DNA pooling based solely upon phenotypic information, or "bulked segregant analysis", has been employed only in the analysis of simply-inherited traits. We have assessed the utility of phenotype-based DNA pools for "tagging" (e.g., identifying DNA markers closely-linked to) quantitative trait loci (QTLs), segregating in the presence of other such loci, and expressing phenotypes which are influenced by the environment. Theoretical estimates suggest that QTL alleles with phenotypic effects of 0.75-1.0 standard deviations (SD), or larger, should be detectable in back-cross (BC), F2 and recombinant inbred (RI) or doubled haploid (DH) populations of manageable size (100-200 plants/lines). However, post hoc analysis of three data sets, used in QTL mapping of tomato and rice, indicate that the majority of QTLs identified had allele effects of less than 0.75 SD, and thus could not be easily tagged in DNA pools. Segregation distortion can have a large effect on the allelic composition of DNA pools, necessitating the use of more individuals in the pools to minimize false positive and false negative results. In general, we suggest that use of phenotype-based DNA pools might be successful in tagging QTLs of very large effect, but is unlikely to permit comprehensive identification of the majority of QTLs affecting a complex trait. DNA pools constructed from a priori information should, however, be useful in identifying new DNA markers for regions of the genome known to contain QTLs.