A protocol with adjuvant chemotherapy (CT) and radiotherapy (RT) for endometrial cancer: Results.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16549-e16549
Author(s):  
Margarita Romeo ◽  
Laia Capdevila ◽  
Sara Cros ◽  
Antoni Tarrats ◽  
Maya Takeuchi ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Statistical Significance ◽  
Acute Diarrhoea ◽  
Phase Iii ◽  
Kaplan Meier ◽  
Key Points ◽  
Phase Iii Trials ◽  
Advanced Stages ◽  
Grade 3

e16549 Background: The classic adjuvant treatment for high-risk endometrial cancer is RT. Several phase III trials explored the role of CT, as single treatment or added to RT sequentially (ST) or concurrently (CR), but design heterogeneity hampers conclusions. We report the results of a single-institution protocol with adjuvant CT + RT for advanced stages or type II histologies. Key points: (1) ST and CR permitted. (2) CT used pre-, post- and/or during RT: carboplatin AUC 5 + paclitaxel 175 mg/m2 (150 during RT) Q3W, 4-6 cycles (“carbotaxol”). (3) since 2010, cisplatin 50 mg/m2 was used for CR (on day 1 and 28 of RT). CR was preceded/followed by carbotaxol. Methods: All patients (PT) included in the protocol between 1/2005 and 9/2011 were retrospectively revised. Endpoints were survival and toxicity grade 3-4. Kaplan Meier and Fisher test were used. Conclusions: CR-carbotaxol showed a longer progression-free and overall survival than ST without reaching statistical significance (log rank, p= 0.14 and p=0.33). Median survivals with CR-cisplatin were not reached because of shorter follow-up. Statistical differences in toxicities were not found. In the CR-carbotaxol arm, 5 PT had grade 3-4 acute diarrhoea vs none in the others. [Table: see text]

Impact of single agent daily prednisone on survival and toxicities in post-docetaxel men with metastatic castration-resistant prostate cancer (mCRPC): An analysis of 2 phase III trials.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 213-213
Author(s):  
Guru Sonpavde ◽  
Gregory Russell Pond ◽  
Arnoud J. Templeton ◽  
Eugene D. Kwon ◽  
Johann S. De Bono
Keyword(s):  
Statistical Significance ◽  
Oral Prednisone ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Multivariable Analysis ◽  
Phase Iii ◽  
Phase Iii Trials ◽  
Grade 3 ◽  
Combination Regimens ◽  
The Impact

213 Background: Daily oral prednisone (P) has been employed for the therapy of mCRPC, alone or in combination regimens. Despite palliative benefits and PSA responses, the overall clinical impact of P is unknown and it may foster resistance mechanisms. We performed a pooled analysis of control arms of randomized trials which either did or did not administer single agent P to evaluate its impact on overall survival (OS) and toxicities. Methods: Individual patient data from control arms ofrandomized trials of post-docetaxel men receiving placebo or P + placebo were eligible for analysis. Patient demographics, survival, and toxicity data were collected. The impact of P on OS and toxicities was investigated in Cox regression models adjusted for known clinical and laboratory prognostic factors. Statistical significance was defined as a p-value < 0.05 and all tests were two-sided. Results: The control arms of 2 randomized phase III trials were available totaling 794 men: the COU-AA-301 trial (n = 394) administered P plus placebo and the CA184-043 trial (n = 400) administered placebo alone. P plus placebo was not significantly associated with OS compared to placebo alone in a multivariable analysis (HR = 0.89 [95% CI 0.72-1.10], p = 0.27). Other factors associated with poor OS were Eastern Cooperative Oncology group (ECOG)-performance status (PS) ≥ 1, Gleason Score ≥ 8, liver metastasis, high PSA, hypoalbuminemia, and elevated LDH.In contrast, CTCAE grade ≥ 3 therapy-related toxicities were significantly increased with P plus placebo compared to placebo alone (HR = 1.48 (1.03-2.13), p = 0.034) in a multivariable analysis. Other baseline factors significantly associated with a higher risk of grade ≥ 3 toxicities were ECOG-PS ≥ 1, hypoalbuminemia and elevated LDH. Conclusions: P plus placebo compared with placebo alone for post-docetaxel men with mCRPC was not associated with extension of OS, but was associated with higher grade ≥ 3 toxicities. With the exception of the use of P in combination with abiraterone, P alone or in combination regimens should be questioned given its unclear palliative benefits and association with increased toxicities.

scholarly journals COVID-19 Vaccine Safety in Cancer Patients: A Single Centre Experience

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3573
Author(s):  
Alfred Chung Pui So ◽  
Harriet McGrath ◽  
Jonathan Ting ◽  
Krishnie Srikandarajah ◽  
Styliani Germanou ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Safety Data ◽  
Vaccine Safety ◽  
Phase Iii ◽  
Solid Malignancy ◽  
Common Grade ◽  
Phase Iii Trials ◽  
Oncology Care ◽  
Grade 3 ◽  
Oncology Centre

Emergency approval of vaccines against COVID-19 provides an opportunity for us to return to pre-pandemic oncology care. However, safety data in cancer patients is lacking due to their exclusion from most phase III trials. We included all patients aged less than 65 years who received a COVID-19 vaccine from 8 December 2020 to 28 February 2021 at our London tertiary oncology centre. Solicited and unsolicited vaccine-related adverse events (VRAEs) were collected using telephone or face-to-face consultation. Within the study period, 373 patients received their first dose of vaccine: Pfizer/BioNTech (75.1%), Oxford/AstraZeneca (23.6%), Moderna (0.3%), and unknown (1.1%). Median follow-up was 25 days (5–85). Median age was 56 years (19–65). Of the patients, 94.9% had a solid malignancy and 76.7% were stage 3–4. The most common cancers were breast (34.0%), lung (13.4%), colorectal (10.2%), and gynaecological (10.2%). Of the patients, 88.5% were receiving anti-cancer treatment (36.2% parenteral chemotherapy and 15.3% immunotherapy), 76.1% developed any grade VRAE of which 2.1% were grade 3. No grade 4/5 or anaphylaxis were observed. The most common VRAEs within 7 days post-vaccination were sore arm (61.7%), fatigue (18.2%), and headaches (12.1%). Most common grade 3 VRAE was fatigue (1.1%). Our results demonstrate that COVID-19 vaccines in oncology patients have mild reactogenicity.

Influence of Gynecologic Oncologists on the Survival of Patients With Endometrial Cancer

2011 ◽  
Vol 29 (7) ◽  
pp. 832-838 ◽  
Author(s):  
John K. Chan ◽  
Alexander E. Sherman ◽  
Daniel S. Kapp ◽  
Ruxi Zhang ◽  
Kathryn E. Osann ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Advanced Disease ◽  
Early Stage ◽  
Multivariable Analysis ◽  
Lower Grade ◽  
Kaplan Meier ◽  
Group A ◽  
Advanced Stages ◽  
Staging Surgery ◽  
Group B

Purpose Despite a lack of evidence for survival benefit, the American College of Obstetrics and Gynecology has recommendations for referral to gynecologic oncologists for the treatment of endometrial cancer. Therefore, we propose to determine the influence of gynecologic oncologists on the treatment and survival of patients with endometrial cancer. Patients and Methods Data were obtained from Medicare and Surveillance, Epidemiology, and End Results (SEER) databases from 1988 to 2005. Kaplan-Meier and Cox proportional hazard methods were used for analyses. Results Of 18,338 women, 21.4% received care from gynecologic oncologists (group A) while 78.6% were treated by others (group B). Women in group A were older (age > 71 years: 49.6% v 44%; P < .001), had more lymph nodes (> 16) removed (22% v 17%; P < .001), presented with more advanced (stages III to IV) cancers (21.9% v 14.6%; P < .001), had higher-grade tumors (P < .001), and were more likely to receive chemotherapy for advanced disease (22.6% v 12.4%; P < .001). In those with stages II to IV disease, the 5-year disease-specific survival (DSS) of group A was 79% versus 73% in group B (P = .001). Moreover, in advanced-stage (III to IV) disease, group A had 5-year DSS of 72% versus 64% in group B (P < .001). However, no association with DSS was identified in stage I cancers. On multivariable analysis, younger age, early stage, lower grade, and treatment by gynecologic oncologists were independent prognostic factors for improved survival. Conclusion Patients with endometrial cancer treated by gynecologic oncologists were more likely to undergo staging surgery and receive adjuvant chemotherapy for advanced disease. Care provided by gynecologic oncologists improved the survival of those with high-risk cancers.

Trial design from a clinical perspective

ESC CardioMed ◽  
2018 ◽  
pp. 3067-3071
Author(s):  
John G. F. Cleland ◽  
Ian Ford
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Trial Design ◽  
Statistical Significance ◽  
Well Being ◽  
Phase Iii ◽  
Practical Significance ◽  
Commercial Company ◽  
Phase Iii Trials ◽  
General Guidance

This chapter is written primarily from the perspective of investigators with limited resources designing clinical trials to assess the effects of interventions on patient well-being and outcomes with the hope that the results might influence clinical practice and guidelines. Other perspectives should be taken into account. The advice may be less applicable when resources are abundant (e.g. phase III trials sponsored by a large commercial company). Much research is funded by commercial companies hoping for a return on investment; they will design clinical trials to increase the chance of a statistically positive result. Many investigators will do the same although their motivation may differ. However, practising clinicians, patients, and health services want trials that help inform their daily clinical practice rather than merely achieving statistical significance. Large studies may be statistically positive but of dubious practical significance. This chapter gives some general guidance on selecting patients, comparators, endpoints, and study design.

Shifting Patterns in the Interpretation of Phase III Clinical Trial Outcomes in Advanced Non–Small-Cell Lung Cancer: The Bar Is Dropping

2014 ◽  
Vol 32 (14) ◽  
pp. 1407-1411 ◽  
Author(s):  
Adrian G. Sacher ◽  
Lisa W. Le ◽  
Natasha B. Leighl
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Statistical Significance ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
End Point ◽  
Phase Iii Trials ◽  
Over Time

Purpose Despite multiple trials of new agents in advanced non–small-cell lung cancer (NSCLC), outcomes remain poor. This study explores how the design and interpretation of randomized trials in advanced NSCLC has changed over time. Methods Phase III randomized controlled trials of systemic therapy for advanced NSCLC between 1980 and 2010 were identified, and their primary end point, outcome, statistical significance, and conclusions were recorded. Results Of 245 trials identified, 203 were eligible for study inclusion. Although overall survival remains the most common primary end point of phase III trials, more trials from the last decade have used progression-free survival instead (none in 1980 to 1990, 13% in 2001 to 2010; P = .002). The percentage of trials meeting their primary statistical end points remained stable over time; however, the percentage of trials reporting a positive outcome without meeting that end point increased (30% in 1980 to 1990, 53% in 2001 to 2010; P < .001). A trend toward decreasing magnitude of survival gain in positive trials was seen over time (3.9 months in 1980 to 1990, 2.5 months in 2001 to 2010; P = .11), with a concomitant increase in the sample size of clinical trials over the same time period (median: 152 patients in 1980 to 1990, 413 in 2001 to 2010; P < .001). Only studies predating 1990 reported negative results as a result of insufficient magnitude of survival benefit despite statistical significance. Conclusion A significant shift has occurred over the past three decades in the design and interpretation of phase III trials in advanced NSCLC. The use of survival as the primary measure of benefit is declining, as is the magnitude of benefit deemed clinically relevant.

Public Availability of Results of Trials Assessing Cancer Drugs in the United States

2013 ◽  
Vol 31 (24) ◽  
pp. 2998-3003 ◽  
Author(s):  
Thi-Anh-Hoa Nguyen ◽  
Agnes Dechartres ◽  
Soraya Belgherbi ◽  
Philippe Ravaud
Keyword(s):  
United States ◽  
The United States ◽  
Phase Iii ◽  
Cancer Drugs ◽  
Randomized Controlled ◽  
Kaplan Meier ◽  
Phase Iii Trials ◽  
Completion Date ◽  
Public Availability ◽  
Over Time

Purpose To evaluate to what extent results of completed trials of cancer drugs conducted in the United States are publicly available at ClinicalTrials.gov, as required by the Food and Drug Administration Amendments Act (FDAAA), or are published in journals. Methods We searched ClinicalTrials.gov for cancer trials governed by the FDAAA: phase II to IV trials assessing drugs in the United States with a primary completion date between December 26, 2007, and May 31, 2010. For each trial, we also searched PubMed to identify the publication of results. We assessed the cumulative percentages of posted or published results over time by using the Kaplan-Meier method. Results We identified 646 trials, including 209 randomized controlled trials (RCTs). At 12 months after completion of the trials, the cumulative percentages of trials with results posted at ClinicalTrials.gov, published in journals, and available either at ClinicalTrials.gov or in journals were 9% (95% CI, 7% to 11%), 12% (95% CI, 10% to 15%), and 20% (95% CI, 17% to 23%), respectively, and for RCTs, the percentages were 12% (95% CI, 8% to 16%), 5% (95% CI, 2% to 8%), and 17% (95% CI, 12% to 22%), respectively. At 36 months, these percentages were 31% (95% CI, 28% to 35%), 35% (95% CI, 31% to 39%), and 55% (95% CI, 51% to 59%), respectively, and for RCTs, they were 38% (95% CI, 31% to 45%), 32% (95% CI, 25% to 39%), and 56% (95% CI, 48% to 62%), respectively. Public availability of phase III trials was 15% (95% CI, 7% to 23%) at 12 months, 39% (95% CI, 27% to 49%) at 24 months, and 64% (95% CI, 50% to 73%) at 36 months. Conclusion Despite the FDAAA, results for nearly half the trials of cancer drugs in the United States were not publicly available 3 years after completion of the trials.

Comparison of the Efficacy and Toxicity of Fludarabine (F) in First Line Therapy of Younger Versus Elderly Patients (Pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Results of a Meta-Analysis of Two Phase III Trials of the German CLL Study Group (GCLLSG).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 717-717 ◽  
Author(s):  
Barbara F. Eichhorst ◽  
Raymonde Busch ◽  
Clemens M. Wendtner ◽  
Michael Hallek ◽  
Keyword(s):  
Age Groups ◽  
The Elderly ◽  
Phase Iii ◽  
First Line ◽  
Two Phase ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials ◽  
Binet Stage ◽  
Grade 3

Abstract Introduction: F based regimen have become the standard treatment in CLL at least in younger pts. However, in elderly pts chlorambucil is still frequently used since it is easy to administer and has less side effects. Here we compare the efficacy and toxicity of F administered to younger pts and elderly pts treated between 1999 and 2004 within two phase III trials of GCLLSG. Patients: 362 pts (median age 59 [range 37–65] years) were randomized to F (n=182) or F plus cyclophosphamide (n=180) within the CLL4 trial. 191 elderly pts (median age 71 [range 65–79] years) were treated with F (92 pts) or chlorambucil (99 pts) within the CLL5 protocol. Inclusion criteria were identical in both trials except for age limits. All pts were previously untreated and in advanced stage Binet C or Binet B with symptoms which require therapy or Binet A with severe B-symptoms. In both studies the F regimen consisted of 30 mg/m2/day (d) IV for 5 consecutive days, every 28 d for up to 6 cycles. Anti-infective prophylaxis and growth factors were not given routinely in both trials. Results: Most of patients in both age groups were in Binet stage B (54% of the younger pts and 52% of the elderly), 35% in each age group were in Binet stage C, 11% and 13% respectively in Binet stage A. No significant difference in the main clinical features was observed except for a higher incidence of concomitant disease in the elderly (61% versus 36%, p=0.001). A mean number of 5.2 F courses was administered in the CLL4 trial and 4.9 courses in the CLL5 trial. The mean administered cumulative dose of F per pt was lower in the elderly pts (1076 mg vs. 1194 mg, p= 0.05). Overall response rates were similar in both arms, with 82.9% in the younger group and 85.7% in the elderly. The complete remission rate was 6.7% in the younger patients and 10.4% in the elderly (p= 0.3). After a follow up time of 24 months (mo) the progression-free survival (PFS) was significantly shorter in the elderly group with 18.7 mo compared to 19.8 mo in the younger group after 22 mo observation time (p=0.03). The overall survival (OS) was significantly impaired in elderly pts as well (29 mo versus median not reached, p&lt;0.001). Progressive disease was the main cause of death in both age groups. In each group 3 treatment related deaths occurred due to infection or hemolysis. The incidence of side effects was similar in both age groups. Severe, CTC grade 3 and 4, myelosuppression occurred in 39% of the younger and 41% of the elderly pts. No difference in the rate of leukocytopenia, thrombocytopenia or anemia was oberved as well. The incidence rate and severity of infections was similar in both groups (24% vs. 32% all and 8.7% vs. 6.9% CTC grade 3 and 4). The incidence of second neoplasia was significantly higher in the elderly pts (2.2% vs. 12.2%, p=0.001). In comparison the prevalence rate of neoplasia in the U.S. population peaks at 11% in the age group of 70–79 (SEER cancer statistic review: 1972–2002). Conclusion: F is a well tolerated treatment regimen in first line therapy of elderly pts with CLL. Response rates were similar in both age groups. PFS and OS were significantly shorter in the elderly population. The incidence of second neoplasia was significantly higher in the elderly pts, but is only slightly increased in comparison to the normal population.

Adding Mercaptopurine and Methotrexate to Alternate Week ATRA Maintenance Therapy Does Not Improve the Outcome for Adults with Acute Promyelocytic Leukemia (APL) in First Remission: Results From North American Leukemia Intergroup Trial C9710

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 258-258 ◽  
Author(s):  
Bayard L. Powell ◽  
Barry K Moser ◽  
Wendy Stock ◽  
Robert E. Gallagher ◽  
Cheryl L Willman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Arsenic Trioxide ◽  
Risk Group ◽  
Statistical Significance ◽  
Phase Iii ◽  
Consolidation Therapy ◽  
Number Of Patients ◽  
First Remission ◽  
Grade 3

Abstract Abstract 258 This randomized phase III clinical trial was designed to evaluate the potential benefit and toxicity of (a) arsenic trioxide (ATO) as initial consolidation therapy and (b) maintenance therapy with oral tretinoin (ATRA) either alone or together with 6-mercaptopurine (MP) and methotrexate (MTX) in newly diagnosed patients with APL. All patients received induction therapy with ATRA, daunorubicin (DNR) and cytarabine. Adults (≥ 15 years) were randomized at study entry to receive a standard consolidation with 2 courses of ATRA plus DNR, or 2 courses of ATO as initial consolidation followed by 2 courses of ATRA plus DNR. Patients who remained in complete remission (CR; n=331) were then randomized (stratified by consolidation arm and age group) to one year of maintenance with ATRA alone (45 mg/m2/d) for 7 days repeated every other week (n=166) or in combination with MP 60 mg/m2/daily plus oral MTX 20 mg/m2/weekly (n=161). The target number of maintenance events was 146, and the study had 80% power to detect a hazard ratio of 1.6 at 5 years. We previously reported that the addition of ATO consolidation markedly improved event-free (EFS) and disease-free (DFS) survival (Blood 2010; 116:3751–3757). We now report the results of the maintenance randomization after a median follow up of 6.2 years. The two groups were well balanced by pretreatment characteristics. DFS, the primary endpoint, and overall survival (OS) were not statistically different for the two maintenance arms (log-rank p=0.14 and p=0.33, respectively). Evaluation by consolidation arm (by intention-to-treat, ITT) and by APL risk group also failed to demonstrate a significant advantage for either maintenance treatment. There was no interaction effect between consolidation and maintenance arms (p=0.78). Age, gender, CD56 expression and FLT3-ITD or TKD mutations at diagnosis did not have an impact on outcome by maintenance arm.ATRA*ATRA/MP/MTX*PDFS: overall41/16630/1610.14DFS by consolidation arm (ITT): ATO10/844/780.13no ATO31/8226/830.21DFS by risk group: low/intermediate25/12819/1300.20high16/3811/310.683-year DFS from CR79%87%0.056OS: overall22/16616/1650.33OS by consolidation arm (ITT): ATO8/843/810.15no ATO14/8213/840.72OS by risk group: low/intermediate14/1289/1340.20high8/387/310.733-year OS from study entry92%95%0.28*Number of events/number of patients in each group or subgroup. No treatment-related deaths were reported during maintenance therapy. Hematologic adverse events were more common in the combination arm (maximum grade 3/4, 18% vs 4%; p< 0.0001), as were non-hematologic adverse events (maximum grade 3/4, 36% vs 25%; p=0.033). Only 71 DFS events have occurred to date. Although the 3-yr DFS favors the combination arm, the differences in DFS and OS with the addition of MP and MTX to ATRA maintenance do not reach statistical significance. The addition of ATO consolidation therapy remains the most important determinant of DFS and OS for APL patients in first remission on this randomized trial. Among patients who were randomized to maintenance, only 5 patients who received ATO consolidation have relapsed – 2 from the combination arm and 3 from the ATRA alone arm. Relapse of APL is uncommon in patients who received ATO consolidation, and the need for any maintenance therapy in these patients has yet to be determined. Disclosures: Off Label Use: Arsenic trioxide as consolidation treatment for APL.

Overexpression of the osteopontin correlates with the aggressiveness of endometrial cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16048-16048
Author(s):  
C. Cho ◽  
S. Cha ◽  
S. Kwon ◽  
Y. Kwon ◽  
S. Kang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Correlation Coefficient ◽  
Statistical Significance ◽  
Endometrial Adenocarcinoma ◽  
Clinicopathologic Characteristics ◽  
Tissue Samples ◽  
Grade 3 ◽  
Endometrial Carcinomas ◽  
Spearman’S Correlation ◽  
Coefficient Method

16048 Background: To test the hypothesis that expression of osteopontin (OPN), an integrin-binding glycoprotein, can independently predict the potential aggressiveness of endometrial cancer. Methods: The status of OPN expression in benign and malignant endometrial cancer cell lines and tissues was analyzed by real time PCR, Western blot, and immunohistochemistry. Nonparametric Spearman's correlation coefficient method was used to assess the statistical significance of the correlation between clinicopathologic characteristics of tumor and OPN expression. Results: An increased expression of OPN was observed in the endometrial cancer compared to normal endometrial tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign endometrial hyperplasia was slightly increased at 1.2, whereas the OPN level in the highly malignant endometrial carcinoma tissue was greatly increased by nearly 3–5 folds. Amongst the 160 cases examined immunohistochemically, of the 43 grade 1 endometrial carcinomas, 31 were unstained and 12 stained weakly positive (+). For the 41 grade 3 or serous type endometrial carcinomas analyzed, 25 (60%) stained strongly positive (+++), 8 (19%) stained moderately positive (++) and 4 (9%) stained weakly positive (+). These results showed that the level of OPN expressed between grade 1 and grade 3 or more was significantly different (Spearman's correlation coefficient method, p = 0.001). However, Kaplan-Meier survival analysis showed that the increased level of OPN expression was not significantly associated with reduced survival time of the patients. Conclusion: The results suggest that the increased OPN level may be involved in the malignant transformation of endometrial adenocarcinoma cells. No significant financial relationships to disclose.

Prognostic value of immunohistochemical phenotypes (IP) of 141 operable breast cancer patients (pts) included in phase III trials of adjuvant therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21040-21040
Author(s):  
R. Trujillo ◽  
E. Gallego ◽  
A. Márquez ◽  
N. Ribelles ◽  
J. Trigo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Phase Iii ◽  
Rank Test ◽  
Prognostic Effect ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Phase Iii Trials ◽  
Her 2

21040 Background: Gene expression arrays and IP studies classified breast cancer in three distinct subtypes: basal, HER2/neu and luminal that are associated with different clinical outcomes. Methods: In 141 pts with operable breast cancer, included in phase III trials of adjuvant therapy in our center, immunohistochemical staining was performed on 3μm sections of paraffin blocks, containing tissue-arrays of tumour tissue.A basal phenotype (BP) was defined by negative estrogen receptor (ER) and progesterone receptor (PR) and positive cytokeratin (CK) 5/6 or EGFR immunoreactivity. HER2/neu phenotype as positive c-erb B2 by HercepTest™ and luminal phenotype (LP) by positive ER, PR and CK 7/8 and negative HER-2. Survival curves were calculated by the Kaplan-Meier method. The differences between survivals were estimated using the log rank test. Multivariate Cox regression analysis was used to evaluate any independent prognostic effect of the variables on disease-free survival (DFS). Results: Complete clinical follow-up information was available for 141 pts. The median follow-up period was 52 months (range 1–103 months). During this period, 13.8% pts died from breast cancer and 27.7% pts relapsed. At the time of the primary diagnosis 10.4% of the pts had lymph node negative disease and 89.6% had positive lymph nodes. 50.8% pts received taxane chemotherapy, 7.7% Trastuzumab, 62.3% radiotherapy and 61% pts received hormonotherapy. Positivity for LP was 65.2%, BP 9.9% and Her-2 phenotype 8.5%. 16.3% didn't fit for any of the three subtypes. Median DFS for BP: 24 moths, for LP and Her-2 phenotypes median DFS was not reached. 5 years DFS were; BP: 19%, LP: 63% and Her-2: 56%. Kaplan-Meier survival analyses demonstrated that the presence of a detectable BP was highly significantly associated with a worse DFS compared with the presence of a LP, log rank test (p= 0.0001). Multivariate Cox regression analyses estimated that the prognostic effect of BP in relation to DFS was independent of lymph node, stage and tumor size, HR: 0.12 95% CI (0.05–0.2). Conclusions: We found that expression of BP was associated with poor prognostic in the context of randomized phase III trials. No significant financial relationships to disclose.

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