Short versus long duration of adjuvant trastuzumab (T) in HER2+ breast cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12057-e12057 ◽  
Author(s):  
Qurat Ul Ain Riaz Sipra ◽  
Irbaz Bin Riaz ◽  
Muhammad Husnain ◽  
Ammad Raina ◽  
Ahsan Khan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Early Stage ◽  
Meta Analysis ◽  
Unmet Need ◽  
Disease Free Survival ◽  
Significant Heterogeneity ◽  
Cardiac Events ◽  
Her2 Breast Cancer ◽  
Study Heterogeneity

e12057 Background: Several RCTs have evaluated a shorter duration of T ( < 12 months) with hopes of similar efficacy, reduced cardiotoxicity, cost and burden of treatment. Of the 5 major studies, PERSPHONE showed that 6 months was non-inferior compared to 12 months. However, four additional studies of shorter duration failed to demonstrate non-inferiority. Therefore, we performed an updated systematic review and a meta-analysis to assess the optimal duration of adjuvant T. Methods: MEDLINE, EMBASE, Cochrane, Scopus and conference proceedings were searched to identify RCTs comparing one year of adjuvant T with a shorter duration in early-stage HER2+ breast cancer. The DerSimonian-Laird random-effects Meta-Analysis was performed using CMAv3 software to derive pooled Hazard Ratio (HR) estimates for overall survival (OS, Disease-Free Survival (DFS) and Odds Ratio(OR) estimates of cardiac toxicity. Q-test was used to assess between-study heterogeneity; I2 statistic was computed to express the percentage of the total observed variability due to study heterogeneity. The risk for bias was assessed using the Cochrane Collaboration’s tool. Results: We screened 1772 citations and identified 5 studies(n = 11,377) for analysis. 5691 patients were randomized to 12 months of adjuvant T while 5686 were randomized to a shorter duration (3 studies evaluated 6 vs 12 months, 2 studies evaluated 9 weeks vs 12 months). OS (HR, 1.16, 95% CI 1.03-1.31, P= 0.015,I2 0.00, p= 0.837) and DFS (HR, 1.14, 95% CI 1.02-1.26 , P = 0.016,I2 14.90, p= 0.319) were significantly worse in patients receiving shorter duration T as compared to 12 months. Cardiotoxicity was significantly higher in the 12 month group vs shorter duration (OR, 2.10, 95% CI 1.58-2.80, p = 0.000 ,I2 51.182, p= 0.085). Grade 3/4 cardiac events and cardiac events leading to discontinuation of therapy were significantly higher in patients receiving 12 months (HR 2.06, 95% CI 1.60-2.63, P = 0.000, I2 3.967, p= 0.384). There was no significant heterogeneity among studies. Risk of bias was low. Conclusions: Twelve months of adjuvant T is associated with significantly better DFS and OS compared to a shorter duration. As such, 12 months should remain the standard of care for most patients. There is an unmet need to identify lower risk groups which might do well with from shorter duration of HER2-directed therapy.

scholarly journals Adjuvant trastuzumab regimen for HER2-positive early-stage breast cancer: a systematic review and meta-analysis

2019 ◽  
Vol 12 (8) ◽  
pp. 815-824 ◽  
Author(s):  
Anne Julienne Genuino ◽  
Usa Chaikledkaew ◽  
Due Ong The ◽  
Thanyanan Reungwetwattana ◽  
Ammarin Thakkinstian
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Early Stage ◽  
Meta Analysis ◽  
Early Stage Breast Cancer ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab

Systematic review of adjuvant therapy for early stage (epithelial) ovarian cancer

2003 ◽  
Vol 13 (4) ◽  
pp. 395-404 ◽  
Author(s):  
B. Winter-Roach ◽  
L. Hooper ◽  
H. Kitchener
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Early Stage ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Significant Difference ◽  
Well Differentiated ◽  
Platinum Chemotherapy

A systematic review and meta analysis has been undertaken in order to evaluate the effectiveness of adjuvant therapy following surgery for early ovarian cancer. Trials reported since 1990 have been of a higher quality enabling a meta analysis of adjuvant chemotherapy vs adjuvant radiotherapy and a meta analysis of adjuvant chemotherapy vs observation. There was no significant difference between radiotherapy and chemotherapy, though these comprised studies which demonstrated considerable heterogeneity. Chemotherapy did confer significant benefit over observation in terms of both overall and disease free survival. Except for women in whom adequate surgical staging has revealed well differentiated disease confined to one or both ovaries with intact capsule, platinum chemotherapy should be offered to reduce risk of recurrence.

Effect of multifocality and multicentricity on outcome in early stage breast cancer: a systematic review and meta-analysis

2014 ◽  
Vol 146 (2) ◽  
pp. 235-244 ◽  
Author(s):  
Francisco E. Vera-Badillo ◽  
Marc Napoleone ◽  
Alberto Ocana ◽  
Arnoud J. Templeton ◽  
Bostjan Seruga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Early Stage ◽  
Meta Analysis ◽  
Early Stage Breast Cancer

A Systematic Review Evaluating the Addition of Radiation Therapy to Chemotherapy for Localized Aggressive Non-Hodgkin’s Lymphoma: What Is the Role for Radiotherapy?.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3155-3155
Author(s):  
Daniel B. Fried ◽  
David E. Morris ◽  
Thomas C. Shea ◽  
Robert Z. Orlowski ◽  
Hendrik W. Van Deventer ◽  
...  
Keyword(s):  
Systematic Review ◽  
Radiation Therapy ◽  
Hodgkin’S Lymphoma ◽  
Randomized Trials ◽  
Early Stage ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Purpose/Objective: We performed a systematic review and meta-analysis of chemotherapy alone compared to chemotherapy plus radiation in the management of adult early stage aggressive non-Hodgkin’s lymphoma (NHL). Overall survival (OS) and disease-free survival (DFS) at 5 years were evaluated. Materials/Methods: Randomized trials published after 1990 comparing chemotherapy alone to chemotherapy plus radiation therapy in the management of adult aggressive NHL were identified through searches of MEDLINE and CANCERLIT databases. In addition, a search of ASTRO, ASCO, and ASH Proceedings from 1999 to the present was performed to identify updates of published articles and abstracts. Studies that were limited to GI sites only were excluded. Only studies employing CHOP or CHOP-like regimens and radiation therapy to a minimum dose of 30 Gy were deemed acceptable. Chemotherapy alone regimens had to consist of a minimum of 4 cycles of therapy. All trials reported OS and DFS at 5 years. A meta-analysis was performed using STATA statistical software, including tests for homogeneity and publication bias. Trials were analyzed by risk ratio (RR) method. Results: Five randomized trials (n = 1933, range for individual studies 215 to 647) were identified that met all inclusion criteria. The 5-yr OS and DFS RRs for the addition of radiation therapy to chemotherapy are presented in Figures 1 and 2, respectively. Three studies suggested an OS and DFS benefit with the addition of radiation to chemotherapy and two suggested an improved OS and DFS among patients treated with chemotherapy alone. Only two of the studies reported patterns of relapse (Aviles et al and Horning et al). These studies showed improved local control with combined modality therapy (16 – 23% vs. 4 – 5%). Risk ratios for OS ranged from 0.90 to 1.56. DFS estimates range from 0.89 to 1.82. A meta-analysis was conducted to estimate the overall treatment effects for this group of studies for both OS and DFS. Due to the high degree of heterogeneity among these trials (p-value for heterogeneity &lt;0.001 for both OS and DFS), summarizing these results with a pooled estimate of effect would be inappropriate. Heterogeneity was decreased only marginally with the exclusion of any individual study from the pooled estimate. Conclusions: It remains unclear whether early stage aggressive NHL patients benefit from the addition of radiation to CHOP-based chemotherapy. However, at this time we are not able to delineate those patients who will benefit from radiotherapy from those who will not. Currently CHOP-based chemotherapy plus radiation remains a standard of care in the US for early stage aggressive NHL. However, controversy remains regarding the role of radiation in light of conflicting results. Our ability to draw firm conclusions based on this review is limited due to the study heterogeneity. Differences among study populations may largely account for this heterogeneity.

Adjuvant radiotherapy (RT) and trastuzumab in stage I-IIA breast cancer: Toxicity data from North Central Cancer Treatment Group Phase III trial N9831

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 523-523 ◽  
Author(s):  
M. Y. Halyard ◽  
T. M. Pisansky ◽  
L. J. Solin ◽  
L. B. Marks ◽  
L. J. Pierce ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Cardiac Events ◽  
Concurrent Administration ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer ◽  
Significant Difference

523 Background: Adjuvant trastuzumab (Herceptin [H]) with chemotherapy improves outcome in HER2+ breast cancer (BC). Preclinical studies suggest H may enhance RT. We herein assess if H given with adjuvant RT increases adverse events (AE) after breast conserving surgery or mastectomy. Methods: N9831 randomized 3505 women with pT1–3N1–2M0, pT2–3N0M0, or pT1cN0M0 (ER/PR negative) HER2+ BC to doxorubicin (A) and cyclophosphamide (C) followed by weekly paclitaxel (T), AC→T→H, or AC→TH→H. Post-lumpectomy breast ± nodal RT was recommended, as was post-mastectomy chest wall + nodal RT (>3 nodes +); internal mammary RT was prohibited. RT started within 5 weeks of completion of T and allowed concurrently with H. 2324 eligible patients were enrolled on study prior to April 25, 2004: 1460 patients receiving RT are available for analysis of RT-associated AEs. Also, 1286 patients on +H arms who completed T (908 +RT and 378 -RT) are available for analysis of clinical cardiac events (CE). Rates of RT-associated AEs were compared across treatment arms, and rates of CE were compared for +RT vs -RT patients within +H arms. All reported p-values are for chi-squared statistics. Results: With a median follow-up of 1.5 years, significant differences among arms in RT-associated AEs were not identified. No significant differences across arms in +RT patients existed in the incidence of skin reaction (p=0.78), pneumonitis (p=0.78), dyspnea (p=0.87), cough (p=0.54), esophageal dysphagia (p=0.26), or neutropenia (p=0.16). There was a significant difference in +RT patients in the incidence of leukopenia (p=0.02) with higher incidence rates in the arms receiving H. RT did not increase the frequency of CE. In the AC→T→H arm, the incidence of CE was 2.2% in +RT patients versus 2.9% in -RT patients. In the AC→TH→H arm, the incidence of CE was 1.5% in +RT patients versus 6.3% in -RT patients. No difference in CE was seen between left- and right-sided RT fields in +RT patients in either +H arm. Conclusion: Concurrent administration of adjuvant RT with H in early stage breast cancer patients is not associated with an increased incidence of acute RT AEs. Further follow-up is required to assess late AEs. No significant financial relationships to disclose.

The impact of time to adjuvant chemotherapy (AC) on survival in colorectal cancer (CRC): A systematic review and meta-analysis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 364-364 ◽  
Author(s):  
J. J. Biagi ◽  
M. Raphael ◽  
W. D. King ◽  
W. Kong ◽  
W. J. Mackillop ◽  
...  
Keyword(s):  
Systematic Review ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Publication Bias ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Significant Heterogeneity ◽  
Risk Of Death ◽  
The Impact ◽  
The Relationship

364 Background: The optimal timing from CRC surgery to initiation of AC is unknown. We report a systematic review and meta-analysis to determine the relationship between time to adjuvant chemotherapy (TTAC) and survival. Methods: A systematic review of literature was done to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. The possible effect of publication bias was investigated using the trim and fill approach. Results: We identified 9 eligible studies involving 14,357 patients (4 published articles, 5 abstracts). Two studies were randomized trials and 7 were cohort studies. Six studies reported TTAC as a binary variable and 3 reported TTAC as ≥3 categories. An estimate of HR for OS was derived from all 9 studies and estimate for DFS was derived from 5 studies. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with a significant decrease in both OS (HR = 1.12, 95% CI 1.09-1.15), and DFS (HR = 1.15, 95% CI 1.11-1.20). The analysis showed no significant heterogeneity among studies. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the two studies of largest weight. Conclusions: This study demonstrates a 12% increase in the risk of death for each 4 week of delay in the start of AC for CRC. These findings indicate the need for clinicians and health systems managers to take the steps necessary to keep TTAC as short as reasonably achievable. In addition, our results suggest there may be some benefit to AC after a 3-month TTAC delay. No significant financial relationships to disclose.

The role of LHRH agonists in ovarian function preservation in premenopausal women undergoing chemotherapy for early stage breast cancer: A systematic review and meta-analysis.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 1050-1050
Author(s):  
Rodrigo Ramella Munhoz ◽  
Allan Andresson Lima Pereira ◽  
Andre Deeke Sasse ◽  
Paulo Marcelo Hoff ◽  
Tiffany A. Traina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Ovarian Function ◽  
Early Stage ◽  
Meta Analysis ◽  
Premenopausal Women ◽  
Early Stage Breast Cancer ◽  
Lhrh Agonists ◽  
Function Preservation
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