Distant disease-free survival (DDFS) according to response category in neoadjuvant endocrine therapy (NET): 6-year analysis in phase III NEOS trial

10531 Background: Letrozole (L) is more active than tamoxifen in early stage ER[+] breast cancer both as adjuvant (BIG-98 trial) or neoadjuvant (LET-024) therapy. However, complete pathological remissions to neoadjuvant endocrine therapy are anecdotal (<5%), there are no new prognostic indicators with clinical implications. Methods: We have review our series of postmenopausal patients with stage II-III breast cancer ER/PgR[+] breast cancer treated in our institution with L as neoadjuvant therapy. All patients had completed 4 months of therapy (in the absence of PD), and had measurable clinical (or radiological) disease. An independent statistical analysis was conducted for disease free (DFS) and distant disease free survival (DDFS). Results: From IV/99 to XII/04, 107 patients fulfill the criteria. Median age 76 years (range 64 to 92); median tumour size 35 mm (range 25 to 100); cT2 75 (70%), cT3/4 32 (30%); cN[-] 83 (78%). The ORR (PR + CR) at 4 months was 63% (7 CR and 60 PR), 4 patients had PD as best response (4%) and 36 a SD (34%). Surgery was done in 63 patients (59%), including all non-responders. Only 2 patients received adjuvant CT. With a median follow-up of 32 month (range 8 to 66), 12 patients had relapsed (9 distant). The 3 years DFS and DDFS were 84% and 90% respectively. In univaried analysis: cN (p < 0.02), cT3/4 (p < 0.02), and clinical response at 4 months (CR) (p = 0.003) were related to DFS; and HER2 (p < 0.05), cN (p < 0.003), and CR (p = 0.007) with DDFS. Other factors like cT, HR-levels, or surgery were not significant. Multivariate analysis showed that only OR and cN remained independently predictive both for DFS and DDFS. Conclusions: Clinical response to neoadjuvant letrozole therapy is an independent predictor of distant disease free survival and could be of value to recommend or deny more aggressive therapies in addition to endocrine therapy. [Table: see text] No significant financial relationships to disclose.

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Impact of clinical response to neoadjuvant endocrine therapy on patient outcomes: a follow-up study of JFMC34-0601 multicentre prospective neoadjuvant endocrine trial

ESMO Open ◽

10.1136/esmoopen-2017-000314 ◽

2018 ◽

Vol 3 (2) ◽

pp. e000314 ◽

Cited By ~ 9

Author(s):

Takayuki Ueno ◽

Shigehira Saji ◽

Norikazu Masuda ◽

Katsumasa Kuroi ◽

Nobuaki Sato ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Response ◽

Endocrine Therapy ◽

Prognostic Value ◽

Disease Free Survival ◽

Long Term Outcomes ◽

Neoadjuvant Endocrine Therapy ◽

Free Survival ◽

Disease Free

BackgroundNeoadjuvant endocrine therapy (NET) has been demonstrated to improve breast-conserving rate and is a widely accepted treatment option for postmenopausal patients with hormone receptor-positive breast cancer. There are few reports on the association of NET response and long-term outcomes.ObjectivesTo investigate the prognostic value of clinical response to NET.MethodsLong-term outcomes of NET were examined in 107 patients who participated in the multicentre prospective neoadjuvant exemestane study, JFMC34-0601. Patients were treated with 25 mg/day exemestane for 16 weeks followed by an 8-week extension depending on the treatment response.ResultsClinical response included partial response (PR) in 58 patients, stable disease in 41 patients and progressive disease (PD) in 8 patients. Clinical response was significantly associated with disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P<0.0001 for all). Especially, patients with PD showed markedly poor outcomes with median DFS=17.8 months (HR (vs PR): 7.7 (95% CI 1.6 to 33)) and median OS=37.7 months (HR (vs PR): 26.3 (95% CI 2.4 to 655)). Preoperative endocrine prognostic index (PEPI) were associated with DFS and marginally with OS (P=0.022 and 0.066, respectively). PEPI=0 indicated an excellent prognosis with 95% 5-year DFS (95% CI 73 to 99). In the multivariate analysis including T stage, nodal status and Ki67, clinical response was an independent prognostic factor for DFS, DDFS and OS (P=0.032, 0.0007 and 0.020, respectively), whereas PEPI was marginally associated with DFS and OS (P=0.079 and 0.068, respectively).ConclusionsClinical response to NET showed an independent prognostic value. Patients with PD had markedly poor prognosis, indicating a need of additional therapy. PEPI=0 indicated an excellent prognosis. The integration of clinical response and PEPI would improve decision-making with regard to treatment options for endocrine-responsive breast cancer when these results are validated in a larger clinical trial.Trial registration numberUMIN C000000345.

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Adjuvant Cyclophosphamide and Docetaxel With or Without Epirubicin for Early TOP2A-Normal Breast Cancer: DBCG 07-READ, an Open-Label, Phase III, Randomized Trial

Journal of Clinical Oncology ◽

10.1200/jco.2017.72.3494 ◽

2017 ◽

Vol 35 (23) ◽

pp. 2639-2646 ◽

Cited By ~ 25

Author(s):

Bent Ejlertsen ◽

Malgorzata K. Tuxen ◽

Erik Hugger Jakobsen ◽

Maj-Britt Jensen ◽

Ann Soegaard Knoop ◽

...

Keyword(s):

Breast Cancer ◽

Disease Free Survival ◽

Normal Breast ◽

Phase Iii ◽

Open Label ◽

Distant Disease ◽

Free Survival ◽

Open Label Phase ◽

Disease Free

Purpose Administration of anthracycline and taxane therapy in the adjuvant setting is considered a standard for breast cancer. We evaluated a non–anthracycline-based regimen in TOP2A-normal patients. Patients and Methods In this multicenter, open-label, phase III trial, 2,012 women with early TOP2A-normal breast cancer and at least one high-risk factor were randomly assigned to receive six cycles of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks (DC) or three cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) followed by three cycles of docetaxel (100 mg/m2; EC-D). The primary end point was disease-free survival (DFS) after a median of 5 years of follow-up. Secondary end points were patient-reported toxicity, overall survival (OS), and distant disease–free survival. Results At a median estimated potential follow-up of 69 months, 5-year DFS was 87.9% (95% CI, 85.6% to 89.8%) in the EC-D arm and 88.3% (95% CI, 86.1% to 90.1%) in the DC arm. There was no significant difference in the risk of DFS events (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00), distant disease–free survival (HR, 1.12; 95% CI, 0.86 to 1.47; P = .40), or mortality (HR, 1.15; 95% CI, 0.83 to 1.59; P = .41) in the intent-to-treat analysis. A significant interaction between menopausal status and treatment group was observed for DFS ( P = .04) but not for OS ( P = .07). Patients with grade 3 tumors derived most benefit from DC, and patients with grade 1 to 2 tumors derived most benefit from EC-D (DFS: interaction P = .02; and OS: interaction P = .03). Patients receiving EC-D reported significantly more stomatitis, myalgia or arthralgia, vomiting, nausea, fatigue, and peripheral neuropathy, whereas edema was more frequent after DC. Conclusion This study provides evidence to support no overall outcome benefit from adjuvant anthracyclines in patients with early TOP2A-normal breast cancer.

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Neoadjuvant rectal score as individual-level surrogate for disease-free survival in rectal cancer in the CAO/ARO/AIO-04 randomized phase III trial

Annals of Oncology ◽

10.1093/annonc/mdy143 ◽

2018 ◽

Vol 29 (7) ◽

pp. 1521-1527 ◽

Cited By ~ 22

Author(s):

E. Fokas ◽

R. Fietkau ◽

A. Hartmann ◽

W. Hohenberger ◽

R. Grützmann ◽

...

Keyword(s):

Rectal Cancer ◽

Disease Free Survival ◽

Phase Iii ◽

Phase Iii Trial ◽

Free Survival ◽

Individual Level ◽

Disease Free

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Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial

Journal of Clinical Oncology ◽

10.1200/jco.2017.76.0355 ◽

2018 ◽

Vol 36 (15) ◽

pp. 1469-1477 ◽

Cited By ~ 54

Author(s):

Thierry André ◽

Dewi Vernerey ◽

Laurent Mineur ◽

Jaafar Bennouna ◽

Jérôme Desrame ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Health Care Providers ◽

Disease Free Survival ◽

Phase Iii ◽

Stage Iii ◽

Care Providers ◽

Free Survival ◽

Stage Iii Colon Cancer ◽

Disease Free

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

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Rationale and description of a lifestyle intervention programme to achieve moderate weight loss in women with non-metastatic breast cancer: the lifestyle intervention part of the SUCCESS C Study

BMJ Nutrition, Prevention & Health ◽

10.1136/bmjnph-2020-000119 ◽

2020 ◽

pp. bmjnph-2020-000119

Author(s):

Dagmar Hauner ◽

Brigitte Rack ◽

Thomas Friedl ◽

Philip Hepp ◽

Wolfgang Janni ◽

...

Keyword(s):

Breast Cancer ◽

Weight Loss ◽

Lifestyle Intervention ◽

Disease Free Survival ◽

Metastatic Breast ◽

Phase Iii ◽

Intervention Programme ◽

Long Term Outcome ◽

Free Survival ◽

Disease Free

ObjectiveThere is growing evidence from observational studies that lifestyle factors such as obesity, an unhealthy diet and lack of physical activity are associated with poor long-term outcome in women with breast cancer. The primary objective of the lifestyle modification part of the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS C) Trial is to investigate the effect of an individualised lifestyle intervention programme aiming at moderate weight loss on disease-free survival in women with HER2/neu-negative breast cancer. Secondary objectives include the effect of the intervention on body weight, cardiovascular risk and quality of life.MethodsThe SUCCESS C Trial is an open-label, multicentre, randomised controlled phase III study using a 2×2 factorial design in women with newly diagnosed HER2/neu-negative intermediate-risk to high-risk breast cancer. The first randomisation served to compare disease-free survival in patients treated with two different chemotherapy regimens (3642 participants). The second randomisation served to compare disease-free survival in patients with a body mass index of 24–40 kg/m² (2292 participants) receiving either a telephone-based individualised lifestyle intervention programme for moderate weight loss or general recommendations for a healthy lifestyle for 2 years. Outcome analyses will be conducted after 5 years of follow-up.PerspectiveThis study will provide information on the efficacy and safety of a comprehensive lifestyle intervention programme on disease-free survival in a large cohort of women with breast cancer. EU Clinical Trials Identifier: 2008-005453-38.

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Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.3.1013 ◽

1997 ◽

Vol 15 (3) ◽

pp. 1013-1021 ◽

Cited By ~ 474

Author(s):

M V Pilepich ◽

R Caplan ◽

R W Byhardt ◽

C A Lawton ◽

M J Gallagher ◽

...

Keyword(s):

Radiation Therapy ◽

Radiation Therapy Oncology Group ◽

Disease Free Survival ◽

Phase Iii ◽

Oncology Group ◽

Phase Iii Trial ◽

Free Survival ◽

Carcinoma Of The Prostate ◽

Androgen Suppression ◽

Disease Free

PURPOSE Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated. MATERIALS AND METHODS In 1987, the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm. RESULTS Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03). CONCLUSION Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.

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48P Association of a genomic index of sensitivity to endocrine therapy with disease-free survival in breast cancer

Annals of Oncology ◽

10.1016/j.annonc.2020.03.182 ◽

2020 ◽

Vol 31 ◽

pp. S32

Author(s):

P. Singh ◽

I. Bedrosian ◽

M.J. Ha ◽

Y. Shen ◽

L. Du ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Disease Free Survival ◽

Free Survival ◽

Disease Free

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A Phase II Trial of 200% ProMACE-CytaBOM in Patients With Previously Untreated Aggressive Lymphomas: Analysis of Response, Toxicity, and Dose Intensity

Blood ◽

10.1182/blood.v94.10.3307.422k11_3307_3314 ◽

1999 ◽

Vol 94 (10) ◽

pp. 3307-3314 ◽

Cited By ~ 25

Author(s):

Leo I. Gordon ◽

Mary Young ◽

Edie Weller ◽

Thomas M. Habermann ◽

Jane N. Winter ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

International Prognostic Index ◽

Disease Free Survival ◽

Dose Intensity ◽

Phase Iii ◽

Aggressive Lymphoma ◽

Hematologic Toxicity ◽

Free Survival ◽

Disease Free

We showed in a phase I trial that the maximum tolerated dose of the ProMACE-CytaBOM regimen in patients with aggressive lymphoma was 200% (Gordon et al, J Clin Oncol 14:1275, 1996). Based on these observations, we initiated a phase II trial designed to determine response, toxicity, and dose intensity using this regimen. We analyzed 74 patients with advanced-stage (III or IV) or bulky stage II aggressive lymphoma. The overall complete response rate was 69% (72% in evaluable patients). With a median follow-up of 4.5 years, the median survival has not yet been reached. The 4-year survival rate is 73% (95% confidence interval [CI] 62, 83%) and no difference was observed among International Prognostic Index (IPI) groups. The 4-year disease-free survival was 71% (95% CI 58, 84%) with no statistical difference between patients with IPI 0 to 1 versus 2 to 4. The toxicity was acceptable, though the grade 4 hematologic toxicity rate for this regimen was 100%. Grade 4 nonhematologic toxicity was 36%. Three cases of either myelodysplastic syndrome or acute leukemia occurred at 7 months, 3.4 years, and 4.2 years after registration. Cytogenic analysis was available in two cases, showing inv(16) without French American British classification (FAB) M4 EO histology in one patient and a 5q-syndrome in the other. These data suggest that 200% ProMACE-CytaBOM with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF results in a high complete remission rate and a disease-free survival comparable to any prior risk-based analysis in aggressive lymphoma. Before using this regimen in general practice, phase III clinical trials should be conducted.

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BIG 1–98: A randomized double-blind phase III study comparing letrozole and tamoxifen given in sequence vs. alone as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.lba528 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. LBA528-LBA528

Author(s):

H. T. Mouridsen ◽

A. Keshaviah ◽

L. Mauriac ◽

J. Forbes ◽

R. Paridaens ◽

...

Keyword(s):

Breast Cancer ◽

Postmenopausal Women ◽

Endocrine Therapy ◽

Disease Free Survival ◽

Adjuvant Endocrine Therapy ◽

Phase Iii ◽

Study Entry ◽

Second Primary ◽

Efficacy Analysis ◽

Disease Free

LBA528 Background: The Primary Core Analysis (PCA) of BIG 1–98 comparing letrozole (L) to tamoxifen (T) as initial adjuvant endocrine therapy showed that L significantly prolonged disease-free survival (DFS), particularly reducing the risk of relapse in distant sites, compared with T for postmenopausal women with endocrine-responsive breast cancer (BC). The aim of the Second Primary Analysis (SPA) is to compare L and T given in sequence vs. alone. On Mar 15, ‘06, the Data Safety Monitoring Committee (DSMC) will review the results of the 2nd interim analysis of the SPA. We will present safety and efficacy data from this analysis if the DSMC recommends release of the results. Methods: 8028 women were randomized upfront to Tx5 years (yrs) (A), Lx5 (B), Tx2→Lx3 (C), or Lx2→Tx3 (D); 1835 to the 2-arm option of the study (arm A vs. B; Mar ’98 - Mar ‘00) and 6193 to the 4-arm option (arm A vs. B vs. C vs. D; Apr ’99 - May ‘03). The primary endpoint was DFS (time from randomization to first occurrence of invasive BC recurrence, invasive contralateral BC, second non-breast malignancy, or death from any cause). The SPA is comprised of two pair-wise comparisons: arm A vs. C and B vs. D. Only 4-arm patients (pts) alive and disease-free at 2 yrs after study entry (corresponding to the treatment switch for arms C and D) are included. These analyses will determine if the risk of an event beyond 2 yrs is reduced by switching agents. Additional exploratory analyses based on all events and follow-up (FU) for 4-arm pts will be conducted, including the comparison of arm B vs. C. The final SPA is planned for Feb ‘08, after 662 events. In Jan ‘05, the 1st interim efficacy analysis was presented to the DSMC, after 162 events among 3641 pts (excluding those who had an event within 2 yrs or did not yet have at least 2 yrs of FU). The median SPA FU (from 2 yrs after study entry) was 11.1 months. The 2nd interim efficacy analysis will be presented to the DSMC on Mar 15, ‘06 based on data received as of a Dec 21, ‘05. Results: Conclusions: No significant financial relationships to disclose.

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