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PO59 DURABLE REMISSIONS WITH TRASTUZUMAB TREATMENT FOR HER2 POSITIVE METASTATIC BREAST CANCER – SINGLE CENTER EXPERIENCE
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Abstracts / The Breast 24 S3 (2015) S21–S75
free survival (PFS), defined as a period from the first therapy cycle administration until disease progression (PD). Statistics included Kaplan Meier test and Log Rank tests). Results: We identified 80 HER2 positive MBC pts treated with firstline trastuzumab therapy in combination with anthracyclines and/ or taxanes (paclitaxel or docetaxel) of median age of 53 years (range 26-74). At the time of diagnosis 35/80 (44%) had early-stage BC, 11/80 pts (14% ) locally advanced BC and 34/80 pts (42%) was diagnosed with metastatic disease. Rebiopsies were done in 17 pts with the confirmation of HER2 positive BC. Eleven out of 80 pts (14%) were treated with firstline trastuzumab in combination with anthracyclines and taxanes and in 69/80 pts (86%) trastuzumab was combined with taxanes only. Median number of docetaxel cycles were 7 (range 4-8) and of weekly paclitaxel were 9 (range 6-12), and after cessation of CT the treatment in pts w/o PD was continued with trastuzumab alone, or trastuzumab with endocrine therapy if HR positive. Among pts diagnosed with stage 1-3 BC 18/46 (39%) received neoadjuvant/adjuvant trastuzumab with average 14 cycles. All patients with ER and/or PR positive BC received adjuvant endocrine therapy. Median number of first-line trastuzumab cycles was 18 (range 2 - 104). Treatment responses were as follows: CR in 9/80 pts (11%), PR in 23/80 pts (29%), SD ≥6 mos in 43/80 pts (54%), and PD as best response had 5/80 (6%) pts. Median PFS for all group of HER2MBC was 18 mos (95%CI 11.13-24.87). There was a significantly reduced PFS for pts previously treated with neoadjuvant/adjuvant trastuzumab in comparison with trastuzumab naive pts (14 mos 95%CI 10.9 – 19.3 vs. 29 mos, 95%CI 38.6–60.1); Log-rank, p<0.01. Conclusion: It seems as if pts with HER2 positive MBC who had been previously treated with neoadjuvant/adjuvant trastuzumab derived less benefit from first-line trastuzumab therapy.
PO59 DURABLE REMISSIONS WITH TRASTUZUMAB TREATMENT FOR HER2 POSITIVE METASTATIC BREAST CANCER – SINGLE CENTER EXPERIENCE Zoran Tomasevic, Zorica Tomasevic, Dobrica Neric, Snezana Milosevic, Bozovic-Spasojevic Ivana, Zdrale Zdravko, Aleksandra Sarcevic, Daniela Kolarevic Institute for Oncology and Radiology of Serbia, Daily Hospital, Belgrade, Serbia and Montenegro Background: Trastuzumab improves response and survival in patients with HER2+ metastatic breast cancer. In this study, we examined patients who had non-progressive disease for at least 2 years after diagnosis of inoperable loco-regional recurrent or metastatic breast cancer under continuous trastuzumab treatment. Primary goal is to assess the longterm outcome of patients with durable response to trastuzumab. Methods: Between 2005 and May 2015, 23 patients with HER2-positive inoperable locally recurrent or metastatic breast cancer and nonprogressive disease for at least 2 years under first line trastuzumab treatment were consecutively documented at the Institute for Oncology and Radiology of Serbia. Treatment was initiated with paclitaxel/ trastuzumab, and continued with trastuzumab ± hormonal treatment after median 18 weekly doses of paclitaxel (16-30). Hormonal treatment is accompanied trastuzumab in 11/23 patients (47.8%). Results: Median age was 53 years. Metastatic disease was diagnosed at initial presentation in 7/23, and at relapse in 16/23 patients. Metastases were present in the liver (6), lungs (5), bones (9), soft tissues (6), CNS (1), and 12/23 patients have multiple locations of metastases. Remission was confirmed in 15/23 patients (65.2%), with 10 complete remissions (43.4%). Median duration of response is 43+ months. The median duration of trastuzumab is 48 months (range 24-120 months+). Progression is confirmed in 4/23 (17.4%) patients; 2 with liver metastases, and 2 with soft tissue metastases. Median duration of trastuzumab treatment in patients with progression was 26 months (25-28). There were no deaths due to metastatic breast cancer at the time of this analysis. There was no cardiac toxicity mandating trastuzumab cessation. Conclusion: Trastuzumab can induce durable responses in a subset of patients with HER2 positive metastatic breast cancer. According to the current recommendations, trastuzumab should be continued until progression.
PO60 THE ROLE OF LAPATINIB IN THE MANAGEMENT OF HER2-POSITIVE METASTATIC BREAST CANCER: A REVIEW OF A SINGLE INSTITUTION’S EXPERIENCE DURING THE TRASTUZUMAB AND LAPATINIB ERA Junichiro Watanabe, Satomo Matsuo Shizuoka Cancer Centre, Breast Oncology Department, Shizuoka, Japan Background: Since new monoclonal antibodies, such as pertuzumab and ado-trastuzumab emtansine, are now being introduced, the practice treating HER2-positive metastatic breast cancer (HER2+MBC) is now changing dramatically. We herein review our experiences during the trastuzumab (TRA) and lapatinib (LAP) era with the aim of evaluating the clinical significance of LAP use in the treatment of HER2+MBC. Patients and Methods: We reviewed our medical records for 140 HER2+MBC patients who were treated between September 2002 and November 2014. The COX regression analyses were applied to identify the risk factors for survival, and the Kaplan-Meier method with a logrank test was utilized to evaluate the overall survival (OS). Results: The characteristics of the 140 HER2+MBC patients were as follows: median age at the diagnosis of MBC, 54 years (range 31-76); primary advanced disease, 43 cases (30.7%), inflammatory appearance, 9 cases (6.4%) and estrogen receptor (ER) positive, 54 cases (38.6%). The metastatic site(s) at the diagnosis of MBC were as follows: lung 43 cases (30.7%); liver 42 cases (30.0%); bone 51 cases (36.4%) and brain 9 cases (6.4%). All patients received TRA-based therapy, and 52 (37.1%) patients received LAP-based regimen(s). Within the observation period, 28 luminal-HER2 and 40 HER2+, for a total of 68 (48.6%) patients, developed brain metastasis (BM), with a median time to BM of 1,612.0 and 1,149.0 days, respectively. The median OS from the diagnosis of HER2+MBC was 1,526.0 days (95% confidence interval [CI], 464.0-4498.0). The multivariate COX regression analyses disclosed that the patients who received a LAP-based regimen, LAP with capecitabine or TRA, had a significantly reduced mortality rate (hazard ratio [HR], 0.42; range 0.27-0.64; p=0.0001), and that this treatment significantly improved their OS (median 2233.0 versus 1199.0 days; p=0.0001) compared to patients who received only TRA-based therapy. The presence of a bone lesion at the time of diagnosis was associated with the patients’ survival (HR, 1.96; range 1.28-3.00; p=0.002); however, the patients’ age, ER status, and the presence of visceral lesions or BM at the diagnosis of HER2+MBC did not. The patients who developed BM during anti-HER2 therapy had increased mortality due to their brain lesion, with a HR of 1.97 (1.26-3.10, p=0.003), however, the use of LAP significantly improved their post-BM survival (median 622.0 days with LAP versus 287.0 days without LAP; P<0.01). Conclusions: According to our institutional review, LAP played a significant role in the management of HER2+MBC in terms of improving the patients’ survival. Various antibody-centered therapies will be the mainstream of HER2+MBC management, however, we conclude LAP will remain a useful treatment option.
PO61 ORAL VINORELBINE IN COMBINATION WITH TRASTUZUMAB AS A FIRST LINE THERAPY OF METASTATIC OR LOCALLY ADVANCED HER2-POSITIVE BREAST CANCER Fadi Farhat3, Joseph Kattan2, Marwan Ghosn1 1Faculty of Medicine- Saint Joseph University, Hematology-Oncology, Beirut, Lebanon; 2Hotel Dieu de France University Hospital, HematologyOncology, Beirut, Lebanon; 3Lebanese University, Hematology-Oncology, Beirut, Lebanon Background: The efficacy of vinorelbine (V) with trastuzumab (T) has shown to be more than just additive in vitro. Moreover, V-T combination proved to be an effective first line treatment for patients (pts) with locally advanced (LA) or metastatic breast cancer (MBC) (HERNATA phase III trial). Oral chemotherapy (CT), preferred by most of the pts, represents a step forward in MBC management with a growing use in
Abstracts / The Breast 24 S3 (2015) S21–S75
free survival (PFS), defined as a period from the first therapy cycle administration until disease progression (PD). Statistics included Kaplan Meier test and Log Rank tests). Results: We identified 80 HER2 positive MBC pts treated with firstline trastuzumab therapy in combination with anthracyclines and/ or taxanes (paclitaxel or docetaxel) of median age of 53 years (range 26-74). At the time of diagnosis 35/80 (44%) had early-stage BC, 11/80 pts (14% ) locally advanced BC and 34/80 pts (42%) was diagnosed with metastatic disease. Rebiopsies were done in 17 pts with the confirmation of HER2 positive BC. Eleven out of 80 pts (14%) were treated with firstline trastuzumab in combination with anthracyclines and taxanes and in 69/80 pts (86%) trastuzumab was combined with taxanes only. Median number of docetaxel cycles were 7 (range 4-8) and of weekly paclitaxel were 9 (range 6-12), and after cessation of CT the treatment in pts w/o PD was continued with trastuzumab alone, or trastuzumab with endocrine therapy if HR positive. Among pts diagnosed with stage 1-3 BC 18/46 (39%) received neoadjuvant/adjuvant trastuzumab with average 14 cycles. All patients with ER and/or PR positive BC received adjuvant endocrine therapy. Median number of first-line trastuzumab cycles was 18 (range 2 - 104). Treatment responses were as follows: CR in 9/80 pts (11%), PR in 23/80 pts (29%), SD ≥6 mos in 43/80 pts (54%), and PD as best response had 5/80 (6%) pts. Median PFS for all group of HER2MBC was 18 mos (95%CI 11.13-24.87). There was a significantly reduced PFS for pts previously treated with neoadjuvant/adjuvant trastuzumab in comparison with trastuzumab naive pts (14 mos 95%CI 10.9 – 19.3 vs. 29 mos, 95%CI 38.6–60.1); Log-rank, p<0.01. Conclusion: It seems as if pts with HER2 positive MBC who had been previously treated with neoadjuvant/adjuvant trastuzumab derived less benefit from first-line trastuzumab therapy.
PO59 DURABLE REMISSIONS WITH TRASTUZUMAB TREATMENT FOR HER2 POSITIVE METASTATIC BREAST CANCER – SINGLE CENTER EXPERIENCE Zoran Tomasevic, Zorica Tomasevic, Dobrica Neric, Snezana Milosevic, Bozovic-Spasojevic Ivana, Zdrale Zdravko, Aleksandra Sarcevic, Daniela Kolarevic Institute for Oncology and Radiology of Serbia, Daily Hospital, Belgrade, Serbia and Montenegro Background: Trastuzumab improves response and survival in patients with HER2+ metastatic breast cancer. In this study, we examined patients who had non-progressive disease for at least 2 years after diagnosis of inoperable loco-regional recurrent or metastatic breast cancer under continuous trastuzumab treatment. Primary goal is to assess the longterm outcome of patients with durable response to trastuzumab. Methods: Between 2005 and May 2015, 23 patients with HER2-positive inoperable locally recurrent or metastatic breast cancer and nonprogressive disease for at least 2 years under first line trastuzumab treatment were consecutively documented at the Institute for Oncology and Radiology of Serbia. Treatment was initiated with paclitaxel/ trastuzumab, and continued with trastuzumab ± hormonal treatment after median 18 weekly doses of paclitaxel (16-30). Hormonal treatment is accompanied trastuzumab in 11/23 patients (47.8%). Results: Median age was 53 years. Metastatic disease was diagnosed at initial presentation in 7/23, and at relapse in 16/23 patients. Metastases were present in the liver (6), lungs (5), bones (9), soft tissues (6), CNS (1), and 12/23 patients have multiple locations of metastases. Remission was confirmed in 15/23 patients (65.2%), with 10 complete remissions (43.4%). Median duration of response is 43+ months. The median duration of trastuzumab is 48 months (range 24-120 months+). Progression is confirmed in 4/23 (17.4%) patients; 2 with liver metastases, and 2 with soft tissue metastases. Median duration of trastuzumab treatment in patients with progression was 26 months (25-28). There were no deaths due to metastatic breast cancer at the time of this analysis. There was no cardiac toxicity mandating trastuzumab cessation. Conclusion: Trastuzumab can induce durable responses in a subset of patients with HER2 positive metastatic breast cancer. According to the current recommendations, trastuzumab should be continued until progression.
PO60 THE ROLE OF LAPATINIB IN THE MANAGEMENT OF HER2-POSITIVE METASTATIC BREAST CANCER: A REVIEW OF A SINGLE INSTITUTION’S EXPERIENCE DURING THE TRASTUZUMAB AND LAPATINIB ERA Junichiro Watanabe, Satomo Matsuo Shizuoka Cancer Centre, Breast Oncology Department, Shizuoka, Japan Background: Since new monoclonal antibodies, such as pertuzumab and ado-trastuzumab emtansine, are now being introduced, the practice treating HER2-positive metastatic breast cancer (HER2+MBC) is now changing dramatically. We herein review our experiences during the trastuzumab (TRA) and lapatinib (LAP) era with the aim of evaluating the clinical significance of LAP use in the treatment of HER2+MBC. Patients and Methods: We reviewed our medical records for 140 HER2+MBC patients who were treated between September 2002 and November 2014. The COX regression analyses were applied to identify the risk factors for survival, and the Kaplan-Meier method with a logrank test was utilized to evaluate the overall survival (OS). Results: The characteristics of the 140 HER2+MBC patients were as follows: median age at the diagnosis of MBC, 54 years (range 31-76); primary advanced disease, 43 cases (30.7%), inflammatory appearance, 9 cases (6.4%) and estrogen receptor (ER) positive, 54 cases (38.6%). The metastatic site(s) at the diagnosis of MBC were as follows: lung 43 cases (30.7%); liver 42 cases (30.0%); bone 51 cases (36.4%) and brain 9 cases (6.4%). All patients received TRA-based therapy, and 52 (37.1%) patients received LAP-based regimen(s). Within the observation period, 28 luminal-HER2 and 40 HER2+, for a total of 68 (48.6%) patients, developed brain metastasis (BM), with a median time to BM of 1,612.0 and 1,149.0 days, respectively. The median OS from the diagnosis of HER2+MBC was 1,526.0 days (95% confidence interval [CI], 464.0-4498.0). The multivariate COX regression analyses disclosed that the patients who received a LAP-based regimen, LAP with capecitabine or TRA, had a significantly reduced mortality rate (hazard ratio [HR], 0.42; range 0.27-0.64; p=0.0001), and that this treatment significantly improved their OS (median 2233.0 versus 1199.0 days; p=0.0001) compared to patients who received only TRA-based therapy. The presence of a bone lesion at the time of diagnosis was associated with the patients’ survival (HR, 1.96; range 1.28-3.00; p=0.002); however, the patients’ age, ER status, and the presence of visceral lesions or BM at the diagnosis of HER2+MBC did not. The patients who developed BM during anti-HER2 therapy had increased mortality due to their brain lesion, with a HR of 1.97 (1.26-3.10, p=0.003), however, the use of LAP significantly improved their post-BM survival (median 622.0 days with LAP versus 287.0 days without LAP; P<0.01). Conclusions: According to our institutional review, LAP played a significant role in the management of HER2+MBC in terms of improving the patients’ survival. Various antibody-centered therapies will be the mainstream of HER2+MBC management, however, we conclude LAP will remain a useful treatment option.
PO61 ORAL VINORELBINE IN COMBINATION WITH TRASTUZUMAB AS A FIRST LINE THERAPY OF METASTATIC OR LOCALLY ADVANCED HER2-POSITIVE BREAST CANCER Fadi Farhat3, Joseph Kattan2, Marwan Ghosn1 1Faculty of Medicine- Saint Joseph University, Hematology-Oncology, Beirut, Lebanon; 2Hotel Dieu de France University Hospital, HematologyOncology, Beirut, Lebanon; 3Lebanese University, Hematology-Oncology, Beirut, Lebanon Background: The efficacy of vinorelbine (V) with trastuzumab (T) has shown to be more than just additive in vitro. Moreover, V-T combination proved to be an effective first line treatment for patients (pts) with locally advanced (LA) or metastatic breast cancer (MBC) (HERNATA phase III trial). Oral chemotherapy (CT), preferred by most of the pts, represents a step forward in MBC management with a growing use in