Magnitude Of Survival Benefit Research Articles

Contemporary survival in metastatic bladder cancer patients: A population-based study.

The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary bladder (mUCUB), is not conclusively studied in either contemporary UCUB patients and/or non-UCUB patients. Within the Surveillance, Epidemiology, and End Results database, contemporary (2017-2020) and historical (2000-2016) systemic therapy-exposed metastatic UCUB and, subsequently, non-UCUB patients were identified. Separate Kaplan-Meier and multivariable Cox regression (CRM) analyses first addressed OS in mUCUB and, subsequently, in metastatic non-UCUB (mn-UCUB). Of 3443 systemic therapy-exposed patients, 2725 (79%) harbored mUCUB versus 709 (21%) harbored mn-UCUB. Of 2725 mUCUB patients, 582 (21%) were contemporary (2017-2020) versus 2143 (79%) were historical (2000-2016). In mUCUB, median OS was 11 months in contemporary versus 8 months in historical patients (Δ = 3 months; p < .0001). After multivariable CRM, contemporary membership status (2017-2020) independently predicted lower overall mortality (OM; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.60-0.76; p < .001). Of 709 mn-UCUB patients, 167 (24%) were contemporary (2017-2020) and 542 (76%) were historical (2000-2016). In mn-UCUB, median OS was 8 months in contemporary versus 7 months in historical patients (Δ = 1 month; p = .034). After multivariable CRM, contemporary membership status (2017-2020) was associated with HR of 0.81 (95% CI = 0.66-1.01; p = .06). In conclusion, contemporary systemic therapy-exposed metastatic patients exhibited better OS in UCUB. However, the magnitude of survival benefit was threefold higher in mUCUB and approximated the survival benefits recorded in prospective randomized trials of novel systemic therapies.

Timing of EGFR or ALK inhibitor initiation and survival among patients with advanced NSCLC.

11148 Background: ALK or EGFR inhibitor is an ideal frontline treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring targetable alteration in ALK or EGFR. However, in the real-world setting, frontline treatment may be delayed or unideal. For such patients, the magnitude of survival benefit when initiating ALK or EGFR inhibitor at a much later timepoint remains unclear. Methods: We utilized a nationwide electronic health record-derived, deidentified database collected from diverse oncology practices across the United States to investigate the timeliness of preferred targeted therapy (PTT), defined as osimertinib, lorlatinib, alectinib or brigatinib. Individualized data obtained from patients with stage IV NSCLC at diagnosis treated with PTT during 2018 to 2023 were analyzed. Timing of PTT initiation was modeled as time-varying covariate. Results: Data from 3250 patients were analyzed: 2640 patients (81%) with EGFR mutation and 610 patients (19%) with ALK rearrangement. The median time to PTT was 7 weeks from diagnosis with 26.4% of patients started PTT within 1 month. Landmark analyses using timepoints ranging from 1 to 12 months after diagnosis showed that at all timepoints, patients who had started on PTT had a significantly better survival than those who had not (Table). In a multivariable analysis, time to PTT ≤ 1 month from diagnosis was an independent predictor of survival: HR 0.74 (95% CI: 0.62-0.89), p=0.002. Prolonged time to PTT was significantly associated with advanced age, positive smoking status and genomic class being ALK as compared to EGFR. Conclusions: In this population-based analysis, an initiation of PTT occurring as late as at least 1 year from diagnosis still resulted in a significant survival benefit, though the magnitude of benefit appeared decreased as time passed. [Table: see text]

Measuring time toxicity of systemic therapies for advanced esophageal and gastric cancers.

e13660 Background: Immunotherapy checkpoint inhibitors have demonstrated clinical benefit in esophago-gastric cancers. Little is known regarding time spent on treatment and adverse events that patients experienced to receive their care, or time toxicity, with regards to advances in immunotherapy. Methods: Fifteen phase 3 trials of anti-PD1 and anti-PDL1 inhibitors used for esophageal and gastric cancers were selected from clinicaltrials.gov if they were published by February 2021. The published methods and protocol were reviewed to estimate the number of ‘hospital days’ based on required procedures associated with screening and treatment related care and proportion of serious and severe adverse events that served as a surrogate for time toxicity. Once hospital days were estimated for all randomized groups, they were analyzed according to immunotherapy arms, which included chemo-immunotherapy and immunotherapy-only arms, and non-immunotherapy arms, which included chemotherapy only and observation arms. Results: From the 15 trials included, there were 32 randomized groups, as 2 trials had 3 randomized groups. Six trials eventually led to FDA approval. Six were for immune checkpoint inhibitors in first line setting, and 8 were in subsequent line setting, and 1 were in adjuvant or maintenance trials. Only pembrolizumab, nivolumab, and avelumab were represented. The median estimated hospital days was 38 days (range 7-52), or 1.3 months, over one year. There was no difference comparing immunotherapy vs. immunotherapy-free arms (p = 0.5), but there was difference comparing chemotherapy vs. chemotherapy-free arms (p &lt; .05). The median survival in the group of patients who received combination chemo-immunotherapy was 13.9 months, with time toxicity of 1.4 months. The survival and time toxicity of the chemotherapy, immunotherapy and placebo arms were 9.1 and 1.3 months, 10 and 0.9 months, and 7.5 and 0.3 months, respectively. Conclusions: While there is substantial number of days committed to cancer therapies among patients with esophageal or gastric cancer, we noticed a trend of more time toxicity in patients who received chemo-immunotherapy, vs patients who received immunotherapy alone. Given the modest improvement in survival gleaned from these trials, the magnitude of survival benefit should be weighed against the time toxicity incurred in patients.

P48.20 Trends in Trial Design, Interpretation and Survival in Phase III Clinical Trials on Extensive-Stage SCLC Between 2000 and 2019

The improvement in the outcomes of patients with extensive-stage small cell lung cancer (SCLC) has been modest over past decades despite tremendous efforts made in optimising treatment outcomes as demonstrated in multiple trials. This review aims to investigate the trends in trial design, interpretation and magnitude of survival benefit described in phase III randomized controlled trials (RCTs) evaluating first-line systemic antineoplastic therapy in patients with extensive-stage SCLC over past two decades. We searched biomedical database for relevant trials published between 2000 and 2019. Descriptive statistics were used to summarize the patterns in trial design and interpretation for each time period (2000-2004, 2005-2009, 2010-2014 and 2015-2019). The Cochran-Armitage trend test was performed to test the changes over time in reporting the primary end point, quality of life (QoL) and trial interpretations. The F test was used to test the change over time in the trial sample size and the reported net survival benefit. The net survival benefit was defined as the difference in median survival time between experimental and control arms. Thirty-eight eligible trials were identified, involving 11,689 patients with 76 treatment arms. Overall survival (OS) was the most common primary end point of trials over the time periods (89% in 2000-2004; 87% in 2005-2009; 80% in 2010-2014; 78% in 2015-2019; P= 0.99). There was a trend toward fewer number of trials that included QoL outcomes (44% in 2000-2004; 60% in 2005-2009; 40% in 2010-2014; 11% in 2015-2019; P= 0.31). Out of the sixteen (42.1%) trials that reported positive conclusions, only seven (18.4%) trials met their primary endpoint; these observations remained stable over time (positive trial conclusion: P= 0.99; trials met their primary endpoint: P= 0.53). The trial sample sizes were increasing over time (median sample size: 154 in 2000-2004; 220 in 2005-2009; 370 in 2010-2014; 299 in 2015-2019; P= 0.08). A trend toward increasing magnitude of survival gain in positive trials was seen over time (1.1 months in 2000-2004; 0.65 months in 2005-2009; 1.6 months in 2010-2014; 2.0 months in 2015-2019; P= 0.92). There was no significant shift in the design, interpretation and survival outcomes of phase III randomized controlled trials of systemic antineoplastic therapy in extensive-stage small cell lung cancer over the past two decades. The use of quality of life outcomes is declining while the improvement in the magnitude of overall survival benefit is modest. More effective systemic agents are needed to improve both the survival and quality of life outcomes of these patients.

Treatment of metastatic castration sensitive prostate cancer (mCSPC) by disease volume: A systematic review and a meta-analysis.

e17539 Background: Chemotherapy with Docetaxel (D) or androgen pathway inhibition (API) with Abiraterone Acetate plus prednisone (AAP), Aplautamide(APA) and Enzalutamide(E) are acceptable, FDA approved treatment options for mCSPC. It is not clear whether the magnitude of benefit varies by the choice of initial agent [chemotherapy vs API] or by volume of disease [High vs Low]. Data is now available from all registration trials by volume status and motivated this analysis to inform initial treatment choice in mCSPC. Methods: We systematically searched MEDLINE(Ovid), Embase, and Scopus for randomized controlled trials of chemotherapy(D) or APIs (AAP, APA, ENZ) that had available hazard ratios (HRs) for overall survival (OS) and Progression Free Survival (PFS) according to patient’s volume of disease. We also reviewed abstracts and presentations from all major conference proceedings. We calculated the pooled overall survival HR and 95% CI by chemotherapy and APIs and by high volume(HVD) and low volume(LVD) using a random effect model, and tested for heterogeneity to assess the null hypothesis that no difference in the survival advantage exists by choice of initial agent and volume of disease. Results: Of 4456 studies identified in our search, there were 8 eligible randomized controlled trials that were included in the analysis. Both D and APIs significantly improved PFS [HR 0.48; 0.45-0.51] and OS [0.72; 0.64-0.81] when added to ADT, however the latter was associated with significantly higher improvement in PFS( P &lt; 0.01) and OS (P = 0.03). In patients treated with D, patients with HVD derive significantly more benefit as compared to LVD( P = 0.046) and patients treated with APIs both HVD and LVD patients derive similar benefit( P = 0.80) (Table). Conclusions: mCSPC patients derive higher magnitude of survival benefit when treated with APIs as compared to D; however, D may be preferred in HVD patients. [Table: see text]

The landscape of immune checkpoint inhibitor plus chemotherapy versus immunotherapy for advanced non-small-cell lung cancer: A systematic review and meta-analysis.

BackgroundLung cancer is the leading cause of cancer‐related deaths worldwide and the prognosis remains poor. The recent introduction of the immune checkpoint inhibitor (ICI), or plus chemotherapy, both resulted in the survival benefit for patients with advanced non‐small‐cell lung cancer (NSCLC), but it remains unanswered which is superior. The current study aimed to estimate the comparative efficacy and safety of ICI‐chemotherapy versus ICI‐monotherapy in advanced NSCLC.MethodsStudies were identified by searching PubMed, Embase, and Cochrane library. The randomized controlled trials (RCTs) that ICI monotherapy or ICI plus chemotherapy compared with chemotherapy in NSCLC were included with available primary endpoints of progression‐free survival (PFS), overall survival (OS), objective response rate, or treatment‐related adverse events. A fixed‐effect or random‐effects model was adopted depending on between‐study heterogeneity.ResultsA total of 20 RCTs involving 12,025 patients with NSCLC were included. Both ICI‐monotherapy and ICI‐chemotherapy resulted in significantly prolonged survival compared to chemotherapy and the former led to significantly longer PFS. The magnitude of survival benefits appeared to be greatest among those treated with pembrolizumab plus platinum‐based chemotherapy (OS, 0.56; PFS, 0.54). Additionally, OS and PFS advantages of ICI therapies were observed in patients with NSCLC with low or high programmed cell death 1 ligand 1 (PD‐L1) expression level, but not in intermediate PD‐L1 TPS.ConclusionsPembrolizumab plus platinum‐based chemotherapy was recommended as the optimal first‐line therapy for advanced patients with NSCLC. Additionally, PD‐L1 alone is not recommended as an adequate molecular biomarker to identify eligible patients for routine clinical practice in immunotherapy.

Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) have shown promising efficacy in the treatment of non‐small cell lung cancer (NSCLC). Sex‐associated dimorphism in immune system response is acknowledged, but the effect of patients’ sex on efficacy of ICIs as treatment in NSCLC still remains controversial. The present study was conducted to investigate the difference in efficacy of NSCLC patients receiving immune checkpoint inhibitors according to the sex. A total of 9583 patients involved 6567 men and 3016 women with advanced lung cancer from 15 randomized controlled trials were included in this study. An overall survival (OS) benefit of immune checkpoint inhibitors was illustrated in both male (HR 0.76, 95% CI 0.71‐0.82) and female (HR 0.73, 95% CI 0.58‐0.91) patients, and a progression‐free survival (PFS) benefit was also found in both men (HR 0.67, 95% CI 0.58‐0.77) and women (HR 0.73, 95% CI 0.56‐0.95) in NSCLC. Both PD‐1/PD‐L1 inhibitors alone and PD‐1/PD‐L1 plus chemotherapy significantly improved the OS and PFS in male patients. Whereas in females, PD‐1 inhibitors or monotherapy significantly benefited the OS but not the PFS, PD‐L1 inhibitors or combination therapy significantly prolonged the PFS but not the OS. No survival benefit was found in both male and female patients from the CTLA‐4 inhibitors. The current study indicated that the magnitude of survival benefit is sex‐dependent and male patients seemed to obtain more consistent and favorable outcomes from ICIs than women patients in NSCLC.

Abstract P3-12-02: Patient prognostic score and survival benefit offered by radiotherapy for ductal carcinoma in situ

Abstract Background: In general, radiotherapy (RT) follows breast-conserving surgery (BCS) and remains the standard of care for the surgical management of both invasive carcinoma and ductal carcinoma in situ (DCIS). Although it is associated with better local control, the magnitude of survival benefit conferred by RT for DCIS has not yet been established. We sought to evaluate whether a survival benefit exists with the addition of RT for patients with DCIS and to validate a patient prognostic score to predict survival benefit. Methods: We performed a retrospective longitudinal cohort study by using the Surveillance Epidemiology and End Results database (SEER 17). Between 1988-2007, we identified 32,144 eligible patients who underwent BCS for DCIS. Using age, year of diagnosis, race, tumor size, hormone receptor status, tumor grade, marital status and SEER region, we calculated propensity score weights to balance clinicopathologic factors between patients receiving only surgery and those receiving surgery and RT. This cohort was divided into seven groups according to the previously validated patient prognostic score proposed by Smith et al. Breast cancer mortality (BCM) was assessed using a log-rank test and a multivariable Cox proportional hazards model. Results: Of 32,144 cases of DCIS, 20,329 cases (63%) were treated with RT (+RT group) and 11,815 cases (37%) were treated with surgery alone (-RT group). There were 304 breast cancer-specific deaths observed over the follow-up period (median 96 months). The weighted cumulative incidence of BCM at ten-years was 1.8% for the +RT group compared to 2.1% for the -RT group (p= 0.003). The effect of RT on survival differed by nuclear grade (p= 0.007), age (p= 0.004), and tumor size (p=0.02). We found that the survival benefit for the +RT group was significantly greater than for the –RT group in subgroups of patients with higher nuclear grade, younger age, and larger tumor size, whereas a statistical reduction of BCM with RT was not observed among patients without these prognostic factors. Moreover, the magnitude of survival benefit was significantly correlated with the patient prognostic score [p&amp;lt;0.0001, Table]. Conclusion: In this population-based cohort study, the patient prognostic score for DCIS accurately estimated the magnitude of survival benefit offered by radiotherapy after BCS, suggesting that decisions for RT could be tailored based on prognostic score and patient preference. Limitations of this study include unmeasured confounders such as a lack of information about patients' comorbidities, margin status and endocrine therapy, and further external validation is needed to confirm our results. Patient Prognostic Score and Hazard Ratio (HR) Comparing Mortality between Radiotherapy Group and non-Radiotherapy GroupPatient Prognostic ScoreNumber of patients in -RT groupNumber of patients in +RT groupWeighted HR of BCM95% CIWeighted HR of OM95% CI078213881.20.67 - 2.10.910.76 - 1.11267744801.00.70 - 1.50.880.78 - 0.992410570800.690.51 - 0.940.710.63 - 0.793304854170.730.48 - 1.10.680.58 - 0.81496517010.310.16 - 0.580.420.30 - 0.5852232480.290.09 - 0.910.430.21 - 0.9161515N.A. N.A. Abbreviation: RT, Radiotherapy; BCM, Breast Cancer Mortality; OM, Overall Mortality: N.A., not available Citation Format: Sagara Y, Freedman RA, Vaz-Luis I, Mallory MA, Wong S, Aydogan F, DeSantis S, Barry WT, Golshan M. Patient prognostic score and survival benefit offered by radiotherapy for ductal carcinoma in situ. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-02.

Abstract S2-06: Survival advantage of anastrozol compared to tamoxifen for lobular breast cancer in the ABCSG-8 study

Abstract Introduction: Invasive lobular cancer (ILC) is the second most common histological type of breast cancer, appearing to have a biology distinct from ductal cancer (IDC). In the first 5 years, the prognosis of ILC seems to be more favourable compared to IDC. The aim of this study was to investigate the differences in benefit from adjuvant Tamoxifen (Tam) and Anastrozol (Ana) for these histologic subtypes. Patients and Methods: The ABCSG-8 (Austrian Breast and Colorectal Cancer Study Group 8) study was a randomized phase III clinical trial (n=3.714) in hormone receptor-positive cancer addressing a sequence strategy with 3 years of Ana after 2 years of Tam in comparison with 5 years of Tam in a low- to intermediate-risk group (Grade 1/2) of postmenopausal patients not receiving adjuvant chemotherapy. Univariate and multivariate comparisons for overall (OS) and disease-free survival (DFS) between endocrine treatments were conducted per subgroup with respect to histology (ductal or lobular). Multivariate Cox analysis included endocrine treatment, histology and their interaction ± additional covariates (age, T-stage, N-stage, grade, ER, PR). For the time-to-event analyses, starting point for all patients was two years after randomization, i.e. when treatment changed from Tamoxifen to Anastrozole on the experimental arm. To avoid crossover effects for post-study treatment, the total time for this analysis is 3 years. Results: The 3-year OS hazard ratio (HR) for Anastrozol versus Tamoxifen in ILC (n=694) was 0.24 (0.08-0.70) vs. IDC (n=2.739) HR 1.08 (0.75-1.58). In multivariate analysis, HR for ILC was 0.23 (0.08-0.68) vs. 1.02 (0.70-1.49) for IDC. The test for interaction of treatment and histology was significant (p=0.01). In ILC, no other clinico-pathologic factor was significantly associated with survival differences compared to IDC, where age, T- and N-stage maintained significance. In the models for DFS, our preliminary analysis after 3-year follow-up did not show significant variations in treatment effect according to histology. Discussion: The magnitude of survival benefit from adjuvant Anastrozol vs. Tamoxifen varies by histology in this large phase III randomized trial. A significant reduction in risk of death occurs only in patients with lobular cancer compared to ductal cancer after only 3 years of follow-up. An updated analysis with additional follow-up will be available at presentation. Citation Format: Michael Knauer, Christine Gruber, Otto Dietze, Richard Greil, Herbert Stöger, Margaretha Rudas, Zsuzsanna Bago-Horvath, Brigitte Mlineritsch, Werner Kwasny, Christian Singer, Peter Dubsky, Raimund Jakesz, Florian Fitzal, Günther Steger, Rupert Bartsch, Martin Filipits, Christian Fesl, Michael Gnant. Survival advantage of anastrozol compared to tamoxifen for lobular breast cancer in the ABCSG-8 study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S2-06.

PCN11 - Magnitude of Benefit and Costs for Recent Solid Tumor Agents

Phase 3 oncology clinical trials have had success rates of 41% (Djulbegovic, Arch Int Med 2008). Against this backdrop, context is needed on the magnitude of benefit to expect from future successful trials, and the interplay of cost. Recognizing the limitations of comparing results across trials and therapies, we assessed recent FDA solid tumor approvals showing overall survival (OS) benefit in a randomized trial. The objective of this analysis is to define the magnitude of benefit and cost of solid tumor therapies approved by FDA from 2009-2013 having phase 3 OS benefit. A systematic review of CenterWatch FDA-Approved Drugs and FDA sNDA/sBLA databases was conducted. Inclusion criteria required FDA approval or efficacy supplement, with OS data published 2009-2013. Hazard ratio (HR) and absolute and relative gain in median OS were assessed. First month drug costs were determined for 4Q2013, using methods previously described by Bach (NEJM 2009). Agents intended to be administered for £ 6 weeks were excluded from the cost analysis. Limitations include omission of many agents that represent important advances yet did not demonstrate statistically significant OS benefit relative to a control arm. 18 FDA approved agents across 25 indications for 9 tumor types were assessed. The mean HR (range) and the mean relative gain in median OS vs trial comparator was 0.702 (0.410-0.817) and 27.91% (11.9%-67.2%), respectively. Medians for each measure were 0.725 and 23.6%. Mean first month treatment costs were $12,601 ($5,881-$50,025) with median costs of $9,282. Over the last 5 years, for FDA-approved agents for treatment of solid tumors, the magnitude of survival benefit, measured either as Hazard Ratio or relative gain in median OS, was 24-30%. This benefit, and first month costs of $9 - 13,000, may represent midpoints of expected levels for future solid tumor agents.

Setting the Bar for Therapeutic Trials in Non–Small-Cell Lung Cancer: How Low Can We Go?

Setting the Bar for Therapeutic Trials in Non–Small-Cell Lung Cancer: How Low Can We Go?

Population-based patterns of palliative systemic therapy use in elderly patients with metastatic colorectal cancer (mCRC).

9547 Background: Elderly cancer patients are consistently under-represented in clinical trials, which may lead to under-treatment. Our aims were to 1) determine the impact of advanced age on use of palliative systemic therapy in mCRC, 2) examine the reasons for treatment choices and 3) compare adverse events and treatment discontinuations in elderly vs young patients. Methods: All patients diagnosed with mCRC from 2006 to 2007 and referred to any 1 of 5 regional cancer centers in British Columbia, Canada were reviewed. Summary statistics were used to describe treatment patterns between elderly patients (EP; &gt;/=70 years) and young patients (YP; &lt;70 years). Cox regression models that adjusted for age and confounders were used to determine the effect of systemic therapy on overall survival (OS). Results: We identified 1,013 patients: median age was 67 years (range 23-93); 42% were elderly and 58% were young; 57% were men; and 66% had ECOG 0/1. Compared to YP, fewer EP were offered systemic therapy (46 vs 76%, p&lt;0.001). Among those treated, EP were less likely than YP to be given combination chemotherapy (47 vs 81%, p&lt;0.001) and bevacizumab (19 vs 47%, p&lt;0.001). Most common reasons for no treatment were similar in EP and YP: patient choice (32% for both), poor ECOG (18% of EP and 16% of YP), and significant comorbidities (11% for both). Advanced age alone was also cited as a reason among EP (7%) for not receiving therapy. In the subset that was treated, risk of adverse events (24 vs 14%, p=0.24) and early treatment discontinuations (14 vs 13%, p=0.88) were comparable between EP and YP, respectively. Receipt of systemic therapy was associated with improved OS in both the elderly (HR for death 0.45, 95% CI 0.37-0.56, p&lt;0.001) and the young (HR for death 0.43, 95% CI 0.35-0.53, p&lt;0.001), regardless of age (p interaction of age and treatment &gt;0.05). Conclusions: In this population-based cohort of mCRC, EP were more likely to receive no treatment, monotherapy rather than combination therapy, or a regimen without bevacizumab. In carefully selected EP, however, it appears that rate of adverse events, frequency of early treatment discontinuations, and magnitude of survival benefit from systemic therapy were comparable to YP.

FOLFIRINOX: A Small Step or a Great Leap Forward?

FOLFIRINOX: A Small Step or a Great Leap Forward?

Number needed to treat (NNT) to compare benefits of letrozole (LET) with adjuvant chemotherapy (CT) in patients (pts) with node-positive (N+) breast cancer (BC)

581 Background: Adjuvant CT is an accepted treatment for N+ BC. The addition of taxanes to anthracycline based adjuvant CT has been demonstrated to improve overall survival (OS) in all but one study as in table below. BIG 1–98 has reported a survival gain with the aromatase inhibitor LET compared to tamoxifen (TAM). NNT (the reciprocal of absolute benefit) is the number of pts that need to be treated with a new intervention to avoid 1 additional event over the benefit provided by standard therapy. For multiple numerical outcomes from randomized trials, NNT is an effective method to express results in a clinically meaningful way. To evaluate the degree of benefit of LET over TAM in women with early stage N+ BC in BIG 1–98, we compared the NNT for survival benefit from LET to that needed to see benefit from the addition of a taxane to anthracycline based CT based on clinical trial data in BC pts with N+ disease. Methods: 5-yr survival data were taken from the pivotal randomized controlled trial (RCT) for LET (N+ pts from BIG 1–98, TAM arm censored for crossover to LET) and from 4 RCTs of adjuvant CT trials, AC-T, FEC-D, and DAC. NNT was calculated with respect to OS at 5 yrs; outcome is presented as the NNT to save a life (see Table). Results: The NNT to save a life for adjuvant LET vs TAM is comparable to the NNT for the addition of a taxane to anthracycline based CT in women with N+ BC. Conclusions: The magnitude of survival benefit of LET over TAM in terms of NNT is comparable to that needed to see a survival benefit from paradigm- changing modern adjuvant CT regimens. F= fluorouracil, E = epirubicin, C = cyclophosphamide, D = docetaxel, T = paclitaxel, A = doxorubicin [Table: see text] [Table: see text]

Association between statin use and mortality in patients with implantable cardioverter-defibrillators and left ventricular systolic dysfunction

A few previous nested cohort trials have evaluated the use of statins on survival and the occurrence of ventricular tachycardia or fibrillation (VT/VF). While the studies generally agreed on the survival effects, they disagreed on the magnitude of the mortality benefit and on the effect on VT/VF. The purpose of this study was to determine in a large, long-term follow-up cohort whether statin therapy could reduce mortality and the occurrence of VT/VF in a mixed population receiving an implantable cardioverter-defibrillator (ICD) for primary or secondary prevention and either ischemic or nonischemic cardiomyopathy. Cohort evaluation of all patients undergoing implantation of an ICD with a left ventricular ejection fraction <40% at an urban U.S. teaching hospital from December 1997 through January 2007. Multivariable analysis of predictors of mortality and VT/VF were conducted. There were 314 deaths among the 1204 patients (26.1%). The use of statin therapy (n = 642) was associated with an adjusted hazard ratio of 0.67 (95% confidence interval [CI] 0.53-0.85; P<.001) for mortality as compared with the no-statin group (n = 562). The use of statin therapy was not associated with a reduction in the adjusted hazard ratio for VT/VF (0.85; 95% CI 0.68-1.06; P = .14). Statin therapy is associated with a reduction in overall mortality in patients with ischemic or nonischemic cardiomyopathy with an ICD implanted for either primary or secondary prevention. The magnitude of survival benefit might have been underestimated given our inability to use statin as a time-dependent covariate.

Radiotherapy of early breast cancer. More than loco-regional tumor control

The authors review the value of radiotherapy in the multidisciplinary treatment of early (stage 0-II) breast cancer and describe past achievements, current scientific evidences and possible future prospects of clinical research. Results of randomized studies proved that conservative surgery with radiotherapy is equally effective to mastectomy for the treatment of in situ and invasive breast cancer, both in terms of local control and overall survival. In the nineties, findings of prospective clinical trials indicate that the use of irradiation in high-risk patients provides both a significant improvement in loco-regional control and survival rate. The magnitude of survival benefit with appropriate patient selection and radiotherapy technique is similar to that seen with adjuvant systemic therapy. Radiotherapy of early breast cancer is based on level I scientific evidences in the vast majority of cases. Remaining controversial issues are subjects of several ongoing international and Hungarian prospective randomized studies.