Review Conference Scene For reprint orders, please contact: [email protected]
2014
36th San Antonio Breast Cancer Symposium: focus on clinical trial results William Jacot*
36th San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 10–14 December 2013
3
ON.14.11
The 2013 San Antonio Breast Cancer Symposium, held under the auspices of the San Antonio Cancer Therapy & Research Center, the AACR, and Baylor College of Medicine, took place in San Antonio (TX, USA) on 10–14 December 2013. This international Symposium was attended by more than 7000 academic and private physicians and researchers from more than 90 countries, involved in all the fields of breast cancer (BC) research and treatment, including basic, translational and clinical research. Topics of discussion covered all aspects of BC research, from basic science to clinical practice, from prevention to targeted therapies. This report will focus on some of the most important results that were presented during the meeting.
uture
Cancer cal trial
ture , UK
Breast cancer prevention Considering the high incidence of breast cancer (BC), prevention of this disease remains a highly debated research field. Jack Cuzick (Queen Mary University of London, London, UK) reported the first results of the International Breast Cancer Intervention Study II (IBIS-II) simultaneously with their publication in The Lancet [1] . This large Phase III trial evaluated the preventive effect of a 5-year anastrozole treatment in 3864 patients aged 40–70 years with BC risk factors. After a 5-year median follow-up, the anastrozole group presented a significantly lower BC incidence compared with the placebo group (2 vs 4%; hazard ratio [HR]: 0.47; 95% CI: 0.32–0.68; p < 0.0001), but no difference in overall survival (18 vs 17 deaths, respectively; p = 0.836). These results are in accordance with the MAP.3 trial [2] , with a significantly longer follow-up. In addition, this study highlighted the high frequency of estrogen deprivation-associated side effects in both groups, with up to 57.8% of patients in the placebo group suffering from musculoskeletal symptoms. However, a better identification of the target population seems necessary, as well as the verification of a reduced BC mortality (not yet achieved) before considering a wider application of this hormone treatment for BC prevention, as discussed in the associated The Lancet editorial by David Cameron [3] .
Keywords
• breast cancer • dose-dense chemotherapy • prevention • targeted therapies
Adjuvant radiation therapy Systematic postoperative radiation therapy after BC surgery remains a standard of care. However, its impact in a population of elderly patients affected by low-risk, node-negative (N0), hormone receptorpositive (HR+) BC remains controversial. Ian Kukler (Western General Hospital, Edinburgh, UK) *Department of Medical Oncology & Translational Research Unit, Institut Régional du Cancer de Montpellier (ICM) – Val d’Aurelle, 208 rue des Apothicaires, 34298 Montpellier Cedex 5, France; Tel.: +33 4 67 61 23 39; Fax: +33 4 67 61 37 06; [email protected]
10.2217/FON.14.11 © 2014 Future Medicine Ltd
Future Oncol. (2014) 10(4), 511–513
part of
ISSN 1479-6694
511
Conference Scene Jacot reported the results of the PRIME II randomized trial, which included 1326 patients to receive whole-breast irradiation (WBI) or no WBI. After a 5-year median follow-up, local control was significantly better with WBI than without (local recurrence of 1.3 vs 4.1%, respectively; p = 0.002). Although no significant difference could be observed in overall survival (94.2 vs 93.8%, respectively; p = 0.24), this study design was not based on this end point, as shown by the relative shortness of the follow-up. Bisphosphonates in early BC treatment Robert Coleman (CR-UK/YCR Sheffield Cancer Research Centre, Sheffield, UK), on behalf of the EBCTCG’s Bisphosphonate Working Group, reported the first meta-analysis of individual patients’ data on this subject. This meta-analysis included 17,791 patients from 36 trials (77% of the whole population of the aforementioned trials) and showed a significant effect of adjuvant bisphosphonates in the postmenopausal population only (34% reduction of bone recurrence: 3.9 vs 5.4%, p = 0.00001; 17% reduction of the 10-year BC mortality: 15.2 vs 18.3%, p = 0.004; 10% reduction of the 10-year all-cause mortality: 21.5 vs 23.8%, p = 0.007). On the same subject, Gunter von Minckwitz from the German Breast Group (Neu-Isenburg, Germany) presented the results of the NATAN trial. This Phase II study evaluated the impact of adjuvant zoledronic acid in patients without pathologic complete response after neoadjuvant chemotherapy. Although the primary end point (5-year overall disease-free survival [DFS]) was not met (HR: 0.96; 95% CI: 0.71–1.30; p = 0.79), a positive trend was observed in the postmenopausal group, in accordance with the aforementioned meta-analysis. HER2-positive breast cancers While bevacizumab is not effective in early triple-negative BC when added to standard adjuvant chemotherapy [4] , its efficacy in early HER2+ BC remains unknown. Denis Salmon (University of California–Los Angeles, CA, USA) reported the primary results of the BETH trial that recruited 3509 patients with N+ or high-risk N0 HER2+ early BCs. This Phase III study assessed the efficacy of an adjuvant trastuzumab and chemotherapy regimen combined or not with a 1-year bevacizumab treatment. The addition of bevacizumab was associated with the same side effects as described in the metastatic
512
Future Oncol. (2014) 10(4)
setting, namely a significant increase of febrile neutropenia, bowel perforation, hypertension, thromboembolism and of other cardiac adverse events. Besides, there was no difference in overall survival or in invasive DFS at 3 years (primary objective – HR: 0.99; 95% CI: 0.79–1.25; p = 0.96). In view of these results, the benefit of adjuvant bevacizumab in early BC treatment seems definitely excluded. However, the adjuvant trastuzumab–chemotherapy combination shows a really promising efficacy, as witnessed by the 3-year invasive DFS of 92% in this high-risk HER2+ population. Indeed, a similar excellent prognosis (as well as safety profile) was reported by Sarah Tonaley (Dana–Farber Cancer Institute, MA, USA) in her presentation on the APT trial. This Phase II study evaluated adjuvant paclitaxel and trastuzumab in patients with N0 and HER2+ BC. One half of the 406 patients presented with small tumors (1–3 cm), while the other half had pT1ab tumors (>3 cm). The 3-year DFS was 98.7% (95% CI: 97.6–99.8), without differences between groups of size (99.5 vs 98.0%, respectively). Considering its great benefit both in terms of prognosis and safety, this paclitaxel–trastuzumab combination could be considered as a serious option for those patients. Although the level of evidence of this APT trial may be deemed insufficient (single arm, nonrandomized), the sample size necessary to design a Phase III trial in this setting would be high. Moreover, a randomization of patients between this regimen and another one could be unethical. It is thus unlikely that results with a higher level of evidence will be available in a near future. Dose-dense adjuvant chemotherapy To date, many questions remain unresolved regarding the impact of dose-dense chemotherapy and of 5-fluorouracil (5-FU) as adjuvant treatment of BC. Francesco Cognetti (Regina Elena National Cancer Institute, Rome, Italy) presented the final results of a Phase III Italian trial in 2091 patients with N+ early BC (
2014
36th San Antonio Breast Cancer Symposium: focus on clinical trial results William Jacot*
36th San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 10–14 December 2013
3
ON.14.11
The 2013 San Antonio Breast Cancer Symposium, held under the auspices of the San Antonio Cancer Therapy & Research Center, the AACR, and Baylor College of Medicine, took place in San Antonio (TX, USA) on 10–14 December 2013. This international Symposium was attended by more than 7000 academic and private physicians and researchers from more than 90 countries, involved in all the fields of breast cancer (BC) research and treatment, including basic, translational and clinical research. Topics of discussion covered all aspects of BC research, from basic science to clinical practice, from prevention to targeted therapies. This report will focus on some of the most important results that were presented during the meeting.
uture
Cancer cal trial
ture , UK
Breast cancer prevention Considering the high incidence of breast cancer (BC), prevention of this disease remains a highly debated research field. Jack Cuzick (Queen Mary University of London, London, UK) reported the first results of the International Breast Cancer Intervention Study II (IBIS-II) simultaneously with their publication in The Lancet [1] . This large Phase III trial evaluated the preventive effect of a 5-year anastrozole treatment in 3864 patients aged 40–70 years with BC risk factors. After a 5-year median follow-up, the anastrozole group presented a significantly lower BC incidence compared with the placebo group (2 vs 4%; hazard ratio [HR]: 0.47; 95% CI: 0.32–0.68; p < 0.0001), but no difference in overall survival (18 vs 17 deaths, respectively; p = 0.836). These results are in accordance with the MAP.3 trial [2] , with a significantly longer follow-up. In addition, this study highlighted the high frequency of estrogen deprivation-associated side effects in both groups, with up to 57.8% of patients in the placebo group suffering from musculoskeletal symptoms. However, a better identification of the target population seems necessary, as well as the verification of a reduced BC mortality (not yet achieved) before considering a wider application of this hormone treatment for BC prevention, as discussed in the associated The Lancet editorial by David Cameron [3] .
Keywords
• breast cancer • dose-dense chemotherapy • prevention • targeted therapies
Adjuvant radiation therapy Systematic postoperative radiation therapy after BC surgery remains a standard of care. However, its impact in a population of elderly patients affected by low-risk, node-negative (N0), hormone receptorpositive (HR+) BC remains controversial. Ian Kukler (Western General Hospital, Edinburgh, UK) *Department of Medical Oncology & Translational Research Unit, Institut Régional du Cancer de Montpellier (ICM) – Val d’Aurelle, 208 rue des Apothicaires, 34298 Montpellier Cedex 5, France; Tel.: +33 4 67 61 23 39; Fax: +33 4 67 61 37 06; [email protected]
10.2217/FON.14.11 © 2014 Future Medicine Ltd
Future Oncol. (2014) 10(4), 511–513
part of
ISSN 1479-6694
511
Conference Scene Jacot reported the results of the PRIME II randomized trial, which included 1326 patients to receive whole-breast irradiation (WBI) or no WBI. After a 5-year median follow-up, local control was significantly better with WBI than without (local recurrence of 1.3 vs 4.1%, respectively; p = 0.002). Although no significant difference could be observed in overall survival (94.2 vs 93.8%, respectively; p = 0.24), this study design was not based on this end point, as shown by the relative shortness of the follow-up. Bisphosphonates in early BC treatment Robert Coleman (CR-UK/YCR Sheffield Cancer Research Centre, Sheffield, UK), on behalf of the EBCTCG’s Bisphosphonate Working Group, reported the first meta-analysis of individual patients’ data on this subject. This meta-analysis included 17,791 patients from 36 trials (77% of the whole population of the aforementioned trials) and showed a significant effect of adjuvant bisphosphonates in the postmenopausal population only (34% reduction of bone recurrence: 3.9 vs 5.4%, p = 0.00001; 17% reduction of the 10-year BC mortality: 15.2 vs 18.3%, p = 0.004; 10% reduction of the 10-year all-cause mortality: 21.5 vs 23.8%, p = 0.007). On the same subject, Gunter von Minckwitz from the German Breast Group (Neu-Isenburg, Germany) presented the results of the NATAN trial. This Phase II study evaluated the impact of adjuvant zoledronic acid in patients without pathologic complete response after neoadjuvant chemotherapy. Although the primary end point (5-year overall disease-free survival [DFS]) was not met (HR: 0.96; 95% CI: 0.71–1.30; p = 0.79), a positive trend was observed in the postmenopausal group, in accordance with the aforementioned meta-analysis. HER2-positive breast cancers While bevacizumab is not effective in early triple-negative BC when added to standard adjuvant chemotherapy [4] , its efficacy in early HER2+ BC remains unknown. Denis Salmon (University of California–Los Angeles, CA, USA) reported the primary results of the BETH trial that recruited 3509 patients with N+ or high-risk N0 HER2+ early BCs. This Phase III study assessed the efficacy of an adjuvant trastuzumab and chemotherapy regimen combined or not with a 1-year bevacizumab treatment. The addition of bevacizumab was associated with the same side effects as described in the metastatic
512
Future Oncol. (2014) 10(4)
setting, namely a significant increase of febrile neutropenia, bowel perforation, hypertension, thromboembolism and of other cardiac adverse events. Besides, there was no difference in overall survival or in invasive DFS at 3 years (primary objective – HR: 0.99; 95% CI: 0.79–1.25; p = 0.96). In view of these results, the benefit of adjuvant bevacizumab in early BC treatment seems definitely excluded. However, the adjuvant trastuzumab–chemotherapy combination shows a really promising efficacy, as witnessed by the 3-year invasive DFS of 92% in this high-risk HER2+ population. Indeed, a similar excellent prognosis (as well as safety profile) was reported by Sarah Tonaley (Dana–Farber Cancer Institute, MA, USA) in her presentation on the APT trial. This Phase II study evaluated adjuvant paclitaxel and trastuzumab in patients with N0 and HER2+ BC. One half of the 406 patients presented with small tumors (1–3 cm), while the other half had pT1ab tumors (>3 cm). The 3-year DFS was 98.7% (95% CI: 97.6–99.8), without differences between groups of size (99.5 vs 98.0%, respectively). Considering its great benefit both in terms of prognosis and safety, this paclitaxel–trastuzumab combination could be considered as a serious option for those patients. Although the level of evidence of this APT trial may be deemed insufficient (single arm, nonrandomized), the sample size necessary to design a Phase III trial in this setting would be high. Moreover, a randomization of patients between this regimen and another one could be unethical. It is thus unlikely that results with a higher level of evidence will be available in a near future. Dose-dense adjuvant chemotherapy To date, many questions remain unresolved regarding the impact of dose-dense chemotherapy and of 5-fluorouracil (5-FU) as adjuvant treatment of BC. Francesco Cognetti (Regina Elena National Cancer Institute, Rome, Italy) presented the final results of a Phase III Italian trial in 2091 patients with N+ early BC (
