Breast Cancer In Neoadjuvant Setting Research Articles

Real World Data of Response of Trastuzumab Based Chemotherapy in Locally Advanced HER2 Positive Breast Cancer from a Developing Country

Background: Data regarding pathologic response of Trastuzumab based chemotherapy in locally advanced HER2 positive breast cancer in neoadjuvant setting is scarce. Methods: A retrospective analysis was conducted from January 2014 to January 2019 at a tertiary cancer care centre in North India and 81 breast cancer patients who underwent neoadjuvant chemotherapy were included. The clinical and pathologic characteristics, response, toxicity and survival data was collected, collated and analyzed. Results: The most commonly observed tumor characteristics at baseline were clinical stage T4 (72.8%), nodal stage N2 (40.7%), invasive ductal carcinoma on histology (98.8%), grade 3 (66.7%) and hormone receptor negativity (54.3%). In terms of post treatment characteristics, a higher incidence of partial response (55.6%), post treatment tumor stage ypT0 (45.7%), nodal status ypN0 (54.3%), absence of extracapsular invasion (77.8%) and absence of pathologic complete response (pCR, 63%) were observed. pCR was attained in 30 patients and was most commonly associated with clinical tumor stage T4 (26/30), nodal stage N2-N3 (19/30), grade 3 (21/30) and hormone receptor negativity (20/30). Altogether, 19.75% had grade 3/4 adverse events. At 6 years, 86% v/s 61% patients were disease free (p=0.037) and 93% v/s 79% patients (p=0.181) were alive in the pCR and no pCR groups, respectively. Conclusion: Even in locally advanced breast cancer (LABC), Trastuzumab had good response in terms of pCR and survival outcomes. Thus, one can be encouraged to use this single HER2 blockade if dual blockade is not feasible in HER2 positive LABC in the neoadjuvant setting.

Four-year follow-up of a phase III study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2-positive early or locally advanced breast cancer in neoadjuvant setting.

578 Background: SB3 was approved in the US and EU as a biosimilar of reference trastuzumab (TRZ). Here, we report 4-year cardiac safety and survival outcomes. Methods: After completing neoadjuvant-adjuvant therapy in patients with HER2 positive early breast cancer, patients from selected countries participated in a 5-year follow-up study of a phase III trial (Pivot et al. Eur J Cancer 2019). The aim was to observe long-term cardiac safety and survival. EFS and OS were analyzed in subgroups by ADCC status within TRZ in ad-hoc analyses. Results: Of 875 patients randomized in the phase III trial, 367 patients (SB3, N=186; TRZ, N=181) were enrolled in the follow-up study. The median follow-up was 53 months. During the follow-up, the incidence of asymptomatic significant left ventricular ejection fraction (LVEF) decrease was low (SB3, n=1; TRZ, n=2), with all patients recovering with LVEF ≥ 50%. No cases of symptomatic congestive heart failure, cardiac death, or other significant cardiac condition were reported. 4-year EFS rates were 83.4% for SB3 and 80.7% for TRZ with a HR of 0.77 [95% CI 0.47, 1.27]. 4-year OS rates were 94.3% for SB3 and 89.6% for TRZ with a HR of 0.53 [95% CI 0.24, 1.16]. From ad-hoc analysis, a difference in EFS and OS was seen between Non-drifted TRZ and Drifted TRZ; Difference between SB3 and Non-drifted TRZ was not statistically significant. Conclusions: In a subset of patients from the phase III trial, comparable long-term cardiac safety and survival at 4-year supports biosimilarity between SB3 and TRZ. Ad-hoc analysis results by ADCC status suggest a possible correlation between ADCC and clinical efficacy. Further follow-up is needed. Clinical trial information: NCT02771795 . [Table: see text]

P156 - 3-year follow-up of a phase III study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2 positive early or locally advanced breast cancer in neoadjuvant setting

P156 - 3-year follow-up of a phase III study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2 positive early or locally advanced breast cancer in neoadjuvant setting

Abstract P6-17-09: Event-free survival by ADCC status from a follow-up study comparing SB3 (trastuzumab biosimilar) with reference trastuzumab for HER2 positive breast cancer in neoadjuvant setting

Abstract Background: SB3 has been approved by the European Commission as a biosimilar of reference trastuzumab (TRZ). Equivalent breast pathologic complete response (bpCR) rate and comparable event-free survival (EFS) and overall survival between SB3 and TRZ have been reported.1-3 Upon monitoring quality attributes of TRZ for the development of SB3, a marked downward shift in antibody-dependent cell-mediated cytotoxicity activities (ADCC) was observed in TRZ lots with expiry dates from Aug 2018 to Dec 2019.4 Some of these lots were used in this study. The objective of this report is to evaluate event-free survival by ADCC status from an additional one-year follow-up study. Methods: Patients with HER2 positive early or locally advanced breast cancer were randomly assigned to receive SB3 or TRZ in neoadjuvant setting concurrently with chemotherapy. Patients then underwent surgery followed by adjuvant SB3 or TRZ. After completion of therapy, patients from selected countries participated in a long-term follow-up study. In TRZ, patients exposed to at least one shifted ADCC lot and those not exposed to shifted ADCC lot during neoadjuvant period were considered as “Exposed” and “Unexposed,” respectively. EFS was defined as the time from the date of randomization to the date when the first event occurred. An event was defined as disease recurrence or progression (local, regional, distant or contralateral) or death due to any cause. EFS after additional one-year follow-up was analyzed by ADCC status in the long-term follow-up set (LFS). Results: A total of 367 patients (SB3, N=186; TRZ, N=181) were included in the LFS. Within TRZ, 55 patients were Unexposed and 126 patients were Exposed. At a median follow-up duration of 30.1 months in SB3 and 30.2 months in TRZ from initiation of study treatment, 4.8% patients in SB3, 3.6% in Unexposed and 10.3% in Exposed experienced events. 4.3% patients in SB3, 1.8% in Unexposed and 9.5% in Exposed experienced recurrence after surgery (Table). Two-year EFS rate was 96.7% in SB3, 98.2% in Unexposed and 92.5% in Exposed. Conclusion: A significantly higher proportion of patients experienced events in Exposed compared to Unexposed (HR 0.07, 95% CI 0.01-0.58, p-value=0.0137). No significant difference in EFS was found between SB3 and Unexposed. Although this study has a relatively short follow-up and has not been powered to evaluate the impact of ADCC on survival, these results suggest a possible correlation between ADCC and clinical efficacy. Further long-term results will follow. Summary of Event-free Survival (LFS) TRZEFS Hazard ratio (95% CI), p-value SB3 N=186All N=181Unexposed N=55Exposed N=126SB3 vs TRZ AllSB3 vs TRZ UnexposedTRZ Unexposed vs TRZ ExposedPatients with event, n (%)9 (4.8%)15 (8.3%)2 (3.6%)13 (10.3%)0.49 (0.21, 1.14) p=0.09751.19 (0.23, 6.18) p=0.83760.07 (0.01, 0.58) p=0.0137Recurrence after surgery8 (4.3%)13 (7.2%)1 (1.8%)12 (9.5%) Progression before surgery1 (0.5%)1 (0.6%)1 (1.8%)0 (0.0%) Death0 (0.0%)1 (0.6%)0 (0.0%)1 (0.8%) Reference: 1. Pivot X et al. J Clin Oncol. 2018; 36:968-74 2. Pivot X et al. Eur J Cancer. 2018; 93:19-27 3. Pivot X et al. J Clin Oncol. 2018; 36 (suppl; abstr e12631) 4. Kim S et al. MAbs. 2017; 9:704-14 Citation Format: Pegram MD, Pivot X, Cortes J, Curigliano G, Yoon Y, Lim J, Song S, Hong E. Event-free survival by ADCC status from a follow-up study comparing SB3 (trastuzumab biosimilar) with reference trastuzumab for HER2 positive breast cancer in neoadjuvant setting [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-09.

Neoadjuvant exemestane for 24 weeks in postmenopausal women with hormone receptor positive stage II or IIIA breast cancer (JFMC34–0601)

591 Background: Exemestane (EXE) is a steroidal aromatase inhibitor and has shown efficacy for not only metastatic breast cancer but also for primary breast cancer situation. Recently it is reported that preoperative treatment with EXE for 24weeks (wks) is more effective than 8 or 16wks. This study aimed to evaluate 24wks treatment of EXE in the neoadjuvant setting for hormone receptor positive, stage II/IIIA, postmenopausal breast cancer. Methods: Stage II/IIIA pts were eligible with confirmed invasive breast cancer and ER/PgR status using needle biopsy. Primary endpoints were ORR and Safety. EXE 25mg/day was administered, and if pts were evaluated CR, PR, SD at 16wks, 8wks treatment was added. Additionally rates of breast conserving surgery (BCS), nodal status, biomarker changes and the relationship between response and survival are being investigated. Results: Between March 2006 and January 2008, 116 pts were enrolled (stage IIA:77%, IIB:20%, III:3%). All pts were ER +, and 80 (69%) were PgR+, and 29 (27.1%) were HER-2+, respectively. At 24 wks, 109pts were evaluable. OR rate was 53% (58/109) and SD rate was 39% (43/109) by investigator's evaluation. Two pts withdrew due to the adverse events. At diagnosis 14 pts would have required mastectomy and after treatment only 5 pts underwent mastectomy. Central pathological review exhibited that biomarker changes during the treatment correlated with tumor response. Conclusions: EXE has shown attractive response for hormone receptor positive breast cancer in neoadjuvant setting. Especially 24wks treatment seems effective with sufficient safety and tolerability. Additional investigations are conducted to explore predictive biomarkers for response and survival. [Table: see text]