- Email: [email protected]
Survival of patients with metastatic breast cancer with or without locoregional therapy
Correspondence
because of disease progression (128 [35%; AIO 0207] and 100 [40%; GERCOR DREAM]). The clinical approach of following induction treatment with a maintenance strategy, and the use of maintenance treatment as a new treatment line, is a new way to manage patients with metastatic colorectal cancer and a new specialty in clinical research. Nevertheless, in all trials done so far—despite all of the differences in trial design and clinical endpoint definitions—active maintenance has benefited patients more than observation, without negatively affecting patients’ quality of life. Therefore, de-escalation maintenance should be regarded as the new standard of care and serve as the control group in trials investigating treatment approaches that are specifically developed as postinduction treatments, such as in GERCOR DREAM or in newer platform trials. We declare no competing interests.
*Susanna Hegewisch-Becker, Ullrich Graeven, Dirk Arnold [email protected] Hope, Practice of Oncology, Hamburg, 20249, Germany (SH-B); Kliniken Maria-Hilf GmbH, Department of Hematology, Oncology and Gastroenterology, Mönchengladbach, Germany (UG); and Klinik für Tumorbiologie, Freiburg, Germany (DA) 1
2
3
4
Hegewisch-Becker S, Graeven U, Lerchenmüller CA, et al. Maintenance strategies after firstline oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 2015; 16: 1355–69. Simkens LHJ, van Tinteren H, May A, et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet 2015; 385: 1843–52. Chibaudel B, Maindrault-Goebel F, Lledo G, et al. Can chemotherapy be discontinued in unresectable metastatic cancer? The GERCOR OPTIMOX2 study. J Clin Oncol 2009; 27: 5727–33. Tournigand C, Chibaudel B, Samson B, et al. Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial. Lancet Oncol 2015; 16: 1493–505.
Survival of patients with metastatic breast cancer with or without locoregional therapy I read with interest the Article by Rajendra Badwe and colleagues,1 an important study on the contribution of locoregional treatment to the outcomes of women presenting with metastatic breast cancer. However, the assertion that locoregional treatment could have an adverse effect on distant progression-free survival is probably an artefact of the censoring strategy, which is evident from inspection of figure 4 in the Article. The figure shows that by 12 months, about 40% of women in the no locoregional treatment group had had locoregional progression and therefore, according to the methods, were censored for future distant events. The authors state in their Discussion that “patients who had both local and distant progression were analysed for both local and distant progression-free survival”. 1 However, this analysis would apply to patients that had simultaneous rather than sequential locoregional and distant progression. A competing-risk analysis or even no censoring at all would have been a more appropriate method to look into whether locoregional treatment has an effect on distant progression. I declare no competing interests.
Ioannis Gounaris [email protected] Cambridge University Hospitals NHS Trust, Oncology, Box 193, Cambridge, Cambridgeshire CB20QQ, UK 1
Badwe R, Hawaldar R, Nair N, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol 2015; 16: 1380–88.
Rajendra Badwe and colleagues 1 describe the results of a single institution, open-label randomised controlled trial comparing the effect
www.thelancet.com/oncology Vol 16 December 2015
of locoregional therapy versus no locoregional therapy of the primary breast tumour in patients with denovo metastatic disease at initial presentation who have responded to first-line chemotherapy. By contrast with many retrospective studies, 2 including a recent meta-analysis, 3 which suggest that patients with de-novo metastatic breast cancer could benefit from locoregional therapy, Badwe and colleagues reported that locoregional therapy does not improve survival in this patient population and was associated with a significant deterioration in terms of distant progression-free survival compared with no locoregional treatment. The median survival of patients in both groups of this study is low, even when compared with survival in the pretargeted therapy era.4 Badwe and colleagues attribute this low survival rate to late diagnosis in Indian patients and challenges faced by resource-poor countries such as financial constraints (eg, 92% of patients with HER2 receptor-positive disease did not receive HER2-targeted therapy). However, the authors did not account for treatment delays between the time of confirmed diagnosis and treatment initiation, which from our experience in Egypt is prevalent in resource-poor countries. A study5 published in 2012 reported that a delay of 60 days or more results in poor outcomes, especially in patients diagnosed with late-stage disease presenting with distant metastasis in low-income communities. 5 These delays could in turn vary the timing of surgery (from time of diagnosis), which the authors acknowledge is a potential confounding factor for survival. More importantly, delays during the administration and planning of locoregional therapy, including radiotherapy, could adversely affect survival by delaying systemic endocrine treatment. This delay in e585
because of disease progression (128 [35%; AIO 0207] and 100 [40%; GERCOR DREAM]). The clinical approach of following induction treatment with a maintenance strategy, and the use of maintenance treatment as a new treatment line, is a new way to manage patients with metastatic colorectal cancer and a new specialty in clinical research. Nevertheless, in all trials done so far—despite all of the differences in trial design and clinical endpoint definitions—active maintenance has benefited patients more than observation, without negatively affecting patients’ quality of life. Therefore, de-escalation maintenance should be regarded as the new standard of care and serve as the control group in trials investigating treatment approaches that are specifically developed as postinduction treatments, such as in GERCOR DREAM or in newer platform trials. We declare no competing interests.
*Susanna Hegewisch-Becker, Ullrich Graeven, Dirk Arnold [email protected] Hope, Practice of Oncology, Hamburg, 20249, Germany (SH-B); Kliniken Maria-Hilf GmbH, Department of Hematology, Oncology and Gastroenterology, Mönchengladbach, Germany (UG); and Klinik für Tumorbiologie, Freiburg, Germany (DA) 1
2
3
4
Hegewisch-Becker S, Graeven U, Lerchenmüller CA, et al. Maintenance strategies after firstline oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 2015; 16: 1355–69. Simkens LHJ, van Tinteren H, May A, et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet 2015; 385: 1843–52. Chibaudel B, Maindrault-Goebel F, Lledo G, et al. Can chemotherapy be discontinued in unresectable metastatic cancer? The GERCOR OPTIMOX2 study. J Clin Oncol 2009; 27: 5727–33. Tournigand C, Chibaudel B, Samson B, et al. Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial. Lancet Oncol 2015; 16: 1493–505.
Survival of patients with metastatic breast cancer with or without locoregional therapy I read with interest the Article by Rajendra Badwe and colleagues,1 an important study on the contribution of locoregional treatment to the outcomes of women presenting with metastatic breast cancer. However, the assertion that locoregional treatment could have an adverse effect on distant progression-free survival is probably an artefact of the censoring strategy, which is evident from inspection of figure 4 in the Article. The figure shows that by 12 months, about 40% of women in the no locoregional treatment group had had locoregional progression and therefore, according to the methods, were censored for future distant events. The authors state in their Discussion that “patients who had both local and distant progression were analysed for both local and distant progression-free survival”. 1 However, this analysis would apply to patients that had simultaneous rather than sequential locoregional and distant progression. A competing-risk analysis or even no censoring at all would have been a more appropriate method to look into whether locoregional treatment has an effect on distant progression. I declare no competing interests.
Ioannis Gounaris [email protected] Cambridge University Hospitals NHS Trust, Oncology, Box 193, Cambridge, Cambridgeshire CB20QQ, UK 1
Badwe R, Hawaldar R, Nair N, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol 2015; 16: 1380–88.
Rajendra Badwe and colleagues 1 describe the results of a single institution, open-label randomised controlled trial comparing the effect
www.thelancet.com/oncology Vol 16 December 2015
of locoregional therapy versus no locoregional therapy of the primary breast tumour in patients with denovo metastatic disease at initial presentation who have responded to first-line chemotherapy. By contrast with many retrospective studies, 2 including a recent meta-analysis, 3 which suggest that patients with de-novo metastatic breast cancer could benefit from locoregional therapy, Badwe and colleagues reported that locoregional therapy does not improve survival in this patient population and was associated with a significant deterioration in terms of distant progression-free survival compared with no locoregional treatment. The median survival of patients in both groups of this study is low, even when compared with survival in the pretargeted therapy era.4 Badwe and colleagues attribute this low survival rate to late diagnosis in Indian patients and challenges faced by resource-poor countries such as financial constraints (eg, 92% of patients with HER2 receptor-positive disease did not receive HER2-targeted therapy). However, the authors did not account for treatment delays between the time of confirmed diagnosis and treatment initiation, which from our experience in Egypt is prevalent in resource-poor countries. A study5 published in 2012 reported that a delay of 60 days or more results in poor outcomes, especially in patients diagnosed with late-stage disease presenting with distant metastasis in low-income communities. 5 These delays could in turn vary the timing of surgery (from time of diagnosis), which the authors acknowledge is a potential confounding factor for survival. More importantly, delays during the administration and planning of locoregional therapy, including radiotherapy, could adversely affect survival by delaying systemic endocrine treatment. This delay in e585