Objective Response to Chemotherapy As a Potential Surrogate End Point of Survival in Metastatic Breast Cancer Patients

Bruzzi, Paolo; Mastro, Lucia Del; Sormani, Maria Pia; Bastholt, Lars; Danova, Marco; Focan, C; Fountzilas, George; Paul, James; Rosso, Riccardo; Venturini, M.

doi:10.1200/jco.2005.02.106

Cited by 112 publications

(82 citation statements)

References 29 publications

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“…For breast cancer, a moderately strong correlation between 2-year disease-free survival and 5-year overall survival was observed in the adjuvant setting (Ng et al, 2008). A meta-analysis of metastatic breast cancer studies found a positive relationship between objective response and overall survival on an individual patient basis, but the relationship was less clear when treatment regimens were compared (Bruzzi et al, 2005). The authors questioned whether the relationship was strong enough to support objective response rate as a valid surrogate of survival when comparing treatments.…”

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confidence: 99%

Relationship between effects on time-to-disease progression and overall survival in studies of metastatic breast cancer

Sherrill

Amonkar

et al. 2008

Br J Cancer

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The relationship between overall survival (OS) and disease progression end points has been demonstrated in colorectal, colon, and non-small cell lung cancers. We assessed the association between OS and time-to-progression (TTP) or progression-free survival (PFS) in metastatic breast cancer (MBC) studies. A literature search retrieved all randomised controlled trials since 1994 in patients with MBC in which OS and either TTP or PFS were reported. Summary data on trial and patient characteristics were abstracted. Study effect sizes were derived as the ratio of median progression (or survival) times, which approximates the hazard ratio. Effects were centred at zero for regression analyses weighted by sample size. Numerous treatments were represented in 67 studies (17 081 patients). Modeling showed a positive association between outcomes for progression and survival (R 2 ¼ 0.30) with a slope of 0.32 (Po0.001) and a non-significant intercept. Thus, a treatment effect on TTP/PFS translated into a concordant effect on OS, but with attenuated effect size. Similar results were found in models of subsets and sensitivity analyses. These results demonstrate that treatment effects on progression end points in MBC trials are expected to result in treatment differences on OS that are smaller yet consistently in the same direction. British Journal of Cancer (2008) Most studies of anticancer agents are designed and powered to show differences between groups on disease progression end points such as response rates, time-to-progression, time-torecurrence or disease-free survival. Although increased survival time is clearly an implicit goal, it is difficult to establish in randomised studies when standard clinical practise is to change treatments at the onset of new progressive events. Especially in the metastatic setting, where expected survival time may be very short, the use of drug combinations or sequential use of multiple drug classes is commonplace. Increasingly, patients in clinical trials are offered alternate treatment upon progression. Consequently, few studies actually demonstrate an unequivocal survival benefit using intent-to-treat analysis approaches.In several tumour types, efforts have been made to justify the use of alternate, more easily established end points by showing how well they are correlated with survival. Several meta-analyses have been published (Table 1) that show a link between time-toprogression (TTP) or progression-free survival (PFS) with overall survival (OS) in metastatic colorectal or non-small cell lung cancer (Johnson et al, 2006) and colon cancer in the adjuvant setting (Sargent et al, 2005). For breast cancer, a moderately strong correlation between 2-year disease-free survival and 5-year overall survival was observed in the adjuvant setting (Ng et al, 2008). A meta-analysis of metastatic breast cancer studies found a positive relationship between objective response and overall survival on an individual patient basis, but the relationship was less clear when treatment regimens were compared...

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confidence: 99%

Relationship between effects on time-to-disease progression and overall survival in studies of metastatic breast cancer

Sherrill

Amonkar

et al. 2008

Br J Cancer

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“…Our results suggest that biomarker DT impact after therapy could be considered as a relevant surrogate marker of survival in progressive MTC treated by pRAIT. Validation of response to a given treatment as a surrogate of survival in a specific cancer condition requires ideally the availability of large datasets of patients randomly assigned to the tested treatment or to a control (34). However, in rare diseases such as MTC, randomized trials are difficult to implement because of the need to include a sufficient number of patients over an acceptable time period.…”

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confidence: 99%

Phase II Trial of Anticarcinoembryonic Antigen Pretargeted Radioimmunotherapy in Progressive Metastatic Medullary Thyroid Carcinoma: Biomarker Response and Survival Improvement

Salaun¹,

Campion²,

Bournaud³

et al. 2012

J Nucl Med

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The prognosis of medullary thyroid carcinoma (MTC) varies from long-to short-term survival based on such prognostic factors as serum calcitonin and carcinoembryonic antigen (CEA) doubling times (DTs). This prospective phase II multicenter trial evaluated the efficacy and safety of anti-CEA pretargeted radioimmunotherapy (pRAIT) in rapidly progressing metastatic MTC patients and also how serum biomarker DTs correlate with clinical outcome. Methods: From June 2004 to January 2008, 42 patients were treated with anti-CEA · anti-diethylenetriaminepentaacetic acid (DTPA) bispecific antibody (hMN-14 · m734) (40 mg/m 2 ), followed by 131 I-di-DTPA-indium bivalent hapten (1.8 GBq/m 2 ) 4-6 d later. Results: The disease control rate (durable stabilization plus objective response) was 76.2%. Grade 3-4 hematologic toxicity was observed in 54.7% of patients and myelodysplastic syndrome in 2, including 1 heavily treated previously. After pRAIT, 21 of 37 assessed patients (56.7%) showed a significant impact on DT ($100% increase of pre-pRAIT calcitonin or CEA DT or prolonged decrease of the biomarker concentration after pRAIT). Pre-pRAIT DT and postpRAIT DT were significant independent predictors for overall survival (OS) from pRAIT (pre-pRAIT: hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.86; P 5 0.016; and postpRAIT: HR, 5.32; 95% CI, 1.63-17.36; P 5 0.006) and OS from diagnosis (pre-pRAIT: HR, 0.21; 95% CI, 0.08-0.51; P 5 0.001; and post-pRAIT: HR, 6.16; 95% CI, 1.81-20.98; P 5 0.004). Conclusion: pRAIT showed antitumor activity, with manageable hematologic toxicity in progressive MTC. Increased biomarker DT after treatment correlated with increased OS.

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“…L'obtention d'une réponse objective semble conduire à un bénéfice en termes de survie (13,14), mais également de réduction des symptômes (15). Cependant, pour la majorité des patientes, il n'est pas démontré que la polychimiothérapie induise une survie supérieure à celle obtenue par monochimiothérapie (16), ce qui conduit plusieurs auteurs à s'interroger sur la meilleure stratégie (17, 18) et certains groupes à recommander une monothérapie (3-5) dans le but notamment de respecter la qualité de vie, hormis le cas des patientes porteuses d'une atteinte viscérale évolutive, nécessitant l'obtention d'une réponse thérapeutique rapide.…”

Section: Traitements En Phase Palliative Activeunclassified

Soins palliatifs: peut-on parler de qualité de vie en phase métastatique?

Kerbrat

Botton

2007

Cancer Du Sein Avancé

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Poser la question sous cette forme paraît impliquer une réponse évidente. L'amélioration de la qualité de vie est un objectif premier de l'activité médi-cale, quelle qu'en soit sa situation : prévention, dépistage, thérapeutique adjuvante ou palliative ; le patient doit pouvoir espérer, sinon tirer, un bénéfice du geste entrepris. L'évaluation des avantages, quels qu'ils soient, doit être contrebalancée par celle des inconvénients.En situation métastatique d'un cancer du sein, cette question peut paraître curieuse dans la mesure où, sauf cas exceptionnel, la patiente ne peut espérer guérir, avec une survie en moyenne inférieure à 3 ans, même si 10 % des malades peuvent espérer une survie supérieure à 10 ans (1). Durant cette période, plusieurs traitements spécifiques, systémiques -chimiothérapie, hormonothérapie, et traitements ciblés -ou locorégionaux -chirurgie, radiothérapie, radiologie interventionnelle -, mais aussi non spécifiques -bisphosphonates, antalgiques, corticoïdes, etc. -seront utilisés.À chaque instant le thérapeute devra, pour la patiente et avec elle, évaluer le rapport coût/bénéfice. Après une réflexion sur les objectifs du traitement, et la définition et la mesure de la qualité de vie, nous séparerons artificiellement deux phases durant cette période, de longueur très variable, une phase « palliative active » où une thérapeutique anticancéreuse sera employée, puis une phase « palliative terminale » proprement dite, avec parfois une frontière difficile à définir ( fig. 1) (2). Objectifs des traitementsIls ont été encore récemment définis en rappelant qu'actuellement le cancer du sein métastatique reste une maladie incurable. Pour le groupe allemand

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Objective Response to Chemotherapy As a Potential Surrogate End Point of Survival in Metastatic Breast Cancer Patients

Cited by 112 publications

References 29 publications

Relationship between effects on time-to-disease progression and overall survival in studies of metastatic breast cancer

Relationship between effects on time-to-disease progression and overall survival in studies of metastatic breast cancer

Phase II Trial of Anticarcinoembryonic Antigen Pretargeted Radioimmunotherapy in Progressive Metastatic Medullary Thyroid Carcinoma: Biomarker Response and Survival Improvement

Soins palliatifs: peut-on parler de qualité de vie en phase métastatique?

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