The author systematically examines one of the important issues of information — establishing the market price. He introduces the concept of «search» — where a buyer wanting to get a better price, is forced to question sellers. The article deals with various aspects of finding the necessary information.

Economics of Information

A b s t r ac t Background Resistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin (mTOR) intracellular signaling pathway. In early studies, the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity. Methods In this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor–positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). The primary end point was progression-free survival. Secondary end points included survival, response rate, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed. Results Baseline characteristics were well balanced between the two study groups. The median age was 62 years, 56% had visceral involvement, and 84% had hormone-sensitive disease. Previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse events were stomatitis (8% in the everolimus-plus-exemestane group vs. 1% in the placebo-plus-exemestane group), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%). At the interim analysis, median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane, according to assessments by local investigators (hazard ratio for progression or death, 0.43; 95% confi dence interval [CI], 0.35 to 0.54; P<0.001). Median progression-free survival was 10.6 months and 4.1 months, respectively, according to central assessment (hazard ratio, 0.36; 95% CI, 0.27 to 0.47; P<0.001). Conclusions Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor–positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors. (Funded by Novartis; BOLERO-2 ClinicalTrials .gov number, NCT00863655.)

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Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer

Background: Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity. However, the role of such mutations in the pathogenesis of lung cancers is unclear. Methods: We sequenced exons 18-21 of the EGFR TK domain from genomic DNA isolated from 617 non-small-cell lung cancers (NSCLCs) and 524 normal lung tissue samples from the same patients and 36 neuroendocrine lung tumors collected from patients in Japan, Taiwan, the United States, and Australia and from 243 other epithelial cancers. Mutation status was compared with clinicopathologic features and with the presence of mutations in KRAS, a gene in the EGFR signaling pathway that is also frequently mutated in lung cancers. All statistical tests were two sided. Results: We detected a total of 134 EGFR TK domain mutations in 130 (21%) of the 617 NSCLCs but not in any of the other carcinomas, nor in nonmalignant lung tissue from the same patients. In NSCLC patients, EGFR TK domain mutations were statistically significantly more frequent in never smokers than ever smokers (51% versus 10%), in adenocarcinomas versus cancer of other histologies (40% versus 3%), in patients of East Asian ethnicity versus other ethnicities (30% versus 8%), and in females versus males (42% versus 14%; all P <.001). EGFR TK domain mutation status was not associated with patient age at diagnosis, clinical stage, the presence of bronchioloalveolar histologic features, or overall survival. The EGFR TK domain mutations we detected were of three common types: in-frame deletions in exon 19, single missense mutations in exon 21, and in-frame duplications/insertions in exon 20. Rare missense mutations were also detected in exons 18, 20, and 21. KRAS gene mutations were present in 50 (8%) of the 617 NSCLCs but not in any tumors with an EGFR TK domain mutation. Conclusions: Mutations in either the EGFR TK domain or the KRAS gene can lead to lung cancer pathogenesis. EGFR TK domain mutations are the first molecular change known to occur specifically in never smokers.

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Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers

Purpose Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non–small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC. Patients and Methods Patients received paclitaxel 225 mg/m2 and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall...

/pdf/gefitinib-in-combination-with-paclitaxel-and-carboplatin-in-21pwcef2cv.pdf

Gefitinib in Combination With Paclitaxel and Carboplatin in Advanced Non–Small-Cell Lung Cancer: A Phase III Trial—INTACT 2

This paper empirically tests and rejects classical competitive theories of wage determination by examining differences in wages for equally skilled workers across industries. Human capital earnings functions are estimated using cross-sectional and longitudinal data from the CPS and QES. The major finding is that the dispersion in wages across industries as measured by the standard deviation in industry wage differentials is substantial. Furthermore, F tests of the joint significance of industry dummy variables are decisively rejected. These differences are very difficult to link to unobserved differences in ability or to compensating differentials for working conditions. Fixed effects models are estimated using two longitudinal data sets to control for constant, unmeasured worker characteristics that might bias cross-sectional estimates. Because measurement error is a serious problem in looking at workers who report changing industries, we use estimates of industry classification error rates to adjust the longitudinal results. In the fixed effects analysis, the industry wage differentials are sizable and are very similar to the cross-sectional estimates. In addition, the fixed effects estimates are robust under a variety of assumptions about classification errors and are similar using both data sets. These findings cast doubt on explanations of industry wage differentials based on unmeasured ability. Additional analysis finds that the industry wage structure is highly correlated for workers in small and large firms, in different regions of the U.S., and with varying job tenures. Finally, evidence is presented demonstrating that turnover has a negative relationship with industry wage differentials. These findings suggest that workers in high wage industries receive noncompetitive rents.

https://www.jstor.org/stable/pdfplus/1911072.pdf

Efficiency wages and the inter-industry wage structure

Purpose: To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer. Patients and Methods: Nine hundred seven patients were randomly assigned letrozole 2.5 mg once daily (453 patients) or tamoxifen 20 mg once daily (454 patients). Patients had estrogen receptor‐ and/or progesterone receptor‐positive tumors, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, rate and duration of clinical benefit, time to treatment failure (TTF), overall survival, and tolerability. Results: TTP was significantly longer for letrozole than for tamoxifen (median, 41 v 26 weeks). Treatment with letrozole reduced the risk of progression by 30% (hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P 5 .0001). TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole (median, 40 v 25 weeks). ORR was higher for letrozole (30% v 20%; P 5 .0006), as was the rate of clinical benefit (49% v 38%; P 5 .001). Survival data are currently immature and not reported here. Both treatments were well tolerated. Conclusion: Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer. J Clin Oncol 19:2596-2606. © 2001 by American Society of Clinical Oncology.

https://ascopubs.org/doi/pdf/10.1200/jco.2001.19.10.2596

Superior E fficacy o f L etrozole V ersus T amoxifen a s First-Line T herapy f or P ostmenopausal W omen W ith Advanced B reast C ancer: R esults o f a P hase I II S tudy o f the I nternational L etrozole B reast C ancer G roup

Purpose: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer. Patients and Methods: This multicenter phase III trial randomly assigned 916 patients with hormone receptor‐ positive or unknown tumors letrozole 2.5 mg (n 458) or tamoxifen 20 mg (n 458) daily until disease progression. Optional cross-over was permitted at the treating physician’s discretion. This report updates efficacy at a median follow-up of 32 months. Results: The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P < .0001), time to treatment failure (median, 9 v 5.7 months, respectively; P < .0001), overall objective response rate (32% v 21%, respectively; P .0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy (“time to chemotherapy”) was significantly longer (P .005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P .001). Conclusion: This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer. J Clin Oncol 21:2101-2109. © 2003 by American Society of Clinical Oncology.

Phase I II S tudy o f L etrozole V ersus T amoxifen a s F irst-Line Therapy o f A dvanced B reast C ancer i n P ostmenopausal Women: A nalysis o f S urvival a nd U pdate o f E fficacy F rom t he International L etrozole B reast C ancer G roup

Pay and Productivity: Wage Determination Within the Firm

165 This and the next four chapters will focus on issues of worker behavior. That is, chapters 6–10 will discuss and analyze various aspects of labor supply behavior. Labor supply decisions can be roughly divided into two categories. The first, which is addressed in this chapter and the next, includes decisions about whether to work at all and, if so, how long to work. Questions that must be answered include whether to participate in the labor force, whether to seek part-time or full-time work, and how long to work both at home and for pay. The second category of decisions, which is addressed in chapters 8–10, deals with the questions that must be faced by a person who has decided to seek work for pay: the occupation or general class of occupations in which to seek offers (chapters 8 and 9) and the geographical area in which offers should be sought (chapter 10). This chapter begins with some basic facts concerning labor force participation rates and hours of work. We then develop a theoretical framework that can be used in the analysis of decisions to work for pay. This framework is also useful for analyzing the structure of various income maintenance programs.

Supply of Labor to the Economy: The Decision to Work

6. If Industry A can substitute capital for labor easily and Industry B can not, then (other things equal) A) Industry A's own-wage elasticity of demand will be higher than Industry B's. B) Industry B's own-wage elasticity of demand will be higher than Industry A's. C) the industries' own-wage elasticities of demand will be equal. D) we cannot predict which firm's own-wage elasticity of demand will be higher.

Robert S. Smith

Papers

Superior E fficacy o f L etrozole V ersus T amoxifen a s First-Line T herapy f or P ostmenopausal W omen W ith Advanced B reast C ancer: R esults o f a P hase I II S tudy o f the I nternational L etrozole B reast C ancer G roup

Phase I II S tudy o f L etrozole V ersus T amoxifen a s F irst-Line Therapy o f A dvanced B reast C ancer i n P ostmenopausal Women: A nalysis o f S urvival a nd U pdate o f E fficacy F rom t he International L etrozole B reast C ancer G roup

Pay and Productivity: Wage Determination Within the Firm

Supply of Labor to the Economy: The Decision to Work

Labor Demand Elasticities