Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer.

INTRODUCTION: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has changed dramatically with the introduction and widespread use of HER2-targeted therapies. There is, however, relatively limited real-world information about the effectiveness and safety of trastuzumab emtansine (T-DM1) in Hong Kong Chinese patients. We assessed the efficacy and toxicity profiles among local patients with HER2-positive advanced breast cancer who had received T-DM1 therapy in the second-line setting and beyond. METHODS: This retrospective study involved five local centres that provide service for over 80% of the breast cancer population in Hong Kong. The study period was from December 2013 to December 2015. Patients were included if they had recurrent or metastatic histologically confirmed HER2+ breast cancer who had progressed after at least one line of anti-HER2 therapy including trastuzumab. Patients were excluded if they received T-DM1 as first-line treatment for recurrent or metastatic HER2+ breast cancer. Patient charts including biochemical and haematological profiles were reviewed for background information, T-DM1 response, and toxicity data. Adverse events were documented during chemotherapy and 28 days after the last dose of medication. RESULTS: Among 37 patients being included in this study, 28 (75.7%) had two or more lines of anti-HER2 agents and 26 (70.3%) had received two or more lines of palliative chemotherapy. Response assessment revealed that three (8.1%) patients had a complete response, eight (21.6%) a partial response, 11 (29.7%) a stable disease, and 12 (32.4%) a progressive disease; three patients could not be assessed. The median duration of response was 17.3 (95% confidence interval, 8.4-24.8) months. The clinical benefit rate (complete response + partial response + stable disease, ≥12 weeks) was 37.8% (95% confidence interval, 22.2%-53.5%). The median progression-free survival was 6.0 (95% confidence interval, 3.3- 9.8) months and the median overall survival had not been reached by the data cut-off date. Grade 3 or 4 toxicities included thrombocytopaenia (13.5%), raised alanine transaminase (8.1%), anaemia (5.4%), and hypokalaemia (2.7%). No patient died as a result of toxicities. CONCLUSIONS: In patients with HER2-positive advanced breast cancer who have been heavily pretreated with anti-HER2 agents and cytotoxic chemotherapy, T-DM1 is well tolerated and provided a meaningful progression-free survival of 6 months and an overall survival that has not been reached. Further studies to identify appropriate patient subgroups are warranted.

Adjuvant S-1 chemotherapy after curative resection of gastric cancer in Chinese patients: assessment of treatment tolerability and associated risk factors.

INTRODUCTION: The use of adjuvant chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) has been shown to improve the outcome of patients with gastric cancer. There are limited data on the tolerability of S-1 in Chinese patients. In this multicentre retrospective study, we assessed the toxicity profile in local patients. METHODS: Patients with stage II-IIIC gastric adenocarcinoma who had undergone curative resection and who had received S-1 adjuvant chemotherapy were included in the study. Patient demographics, tumour characteristics, chemotherapy records, as well as biochemical, haematological, and other toxicity profiles were extracted from medical charts. Potential factors associated with grade 2-4 toxicities were identified. RESULTS: Adjuvant S-1 was administered to 30 patients. Overall, 19 (63%) patients completed eight cycles. The most common grade 3-4 adverse events included neutropaenia (10%), anaemia (6.7%), septic episode (16.7%), diarrhoea (6.7%), hyperbilirubinaemia (6.7%), and syncope (6.7%). Dose reductions were made in 22 (73.3%) patients and 12 (40.0%) patients had dose delays. Univariate analyses showed that patients who underwent total gastrectomy were more likely to experience adverse haematological events (P=0.034). Patients with nodal involvement were more likely to report adverse non-haematological events (P=0.031). Patients with a history of regular alcohol intake were more likely to have earlier treatment withdrawal (P=0.044). Lower body weight (P=0.007) and lower body surface area (P=0.017) were associated with dose interruptions. CONCLUSIONS: The tolerability of adjuvant S-1 in our patient population was similar to that in other Asian patient populations. The awareness of S-1-related toxicities and increasing knowledge of potential associated factors may enable optimisation of S-1 therapy.

Clinical outcome of neoadjuvant chemoradiation in locally advanced rectal cancer at a tertiary hospital.

OBJECTIVES: To review the clinical outcome of locally advanced rectal cancer treated with neoadjuvant chemoradiation followed by definitive surgery with or without adjuvant chemotherapy and to elucidate the prognostic factors for treatment outcome. METHODS: This historical cohort study was conducted at a tertiary public hospital in Hong Kong. All patients who had undergone neoadjuvant chemoradiation for locally advanced rectal cancer in our department from November 2005 to October 2014 were recruited. Local recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival of patients were documented. RESULTS: A total of 135 patients who had received neoadjuvant chemoradiation during the study period were reviewed. There were 130 patients who had completed neoadjuvant chemoradiation and surgery. The median follow-up time was 35.1 months. The 3- and 5-year local recurrence-free survival, distant metastasis-free survival, disease-free survival, as well as overall survival rates were 91.8% and 86.7%, 73.9% and 72.1%, 70.1% and 64.6%, as well as 86.5% and 68.4%, respectively. The rate of pathological complete response was 13.8%. The T and N downstaging rate was 49.2% and 63.1%, respectively. The rate of conversion from threatened circumferential resection margin to clearance of margin was 90.6%. Of the 42 cases that were initially deemed to require abdominal perineal resection, 15 (35.7%) were converted to sphincter-sparing surgery. CONCLUSIONS: The treatment outcome of neoadjuvant chemoradiation for locally advanced rectal cancer was comparable with overseas data in terms of local control rate and overall survival. This strategy may increase the chance of achieving a clear surgical margin by downstaging the tumour, especially in patients who presented with threatened circumferential margin.

Does primary tumour volumetry performed early in the course of definitive concomitant chemoradiotherapy for head and neck squamous cell carcinoma improve prediction of primary site outcome?

Although previous studies have documented correlations between pre-treatment or post-treatment primary tumour volumes and local outcome following definitive concomitant chemoradiotherapy (CCRT) in head and neck squamous cell carcinoma (HNSCC), no study has included and compared tumour volumes during CCRT. We reviewed the MRIs of 69 HNSCC patients treated with a 6 weeks course of CCRT and who underwent successful MRI pre-treatment (n = 69), 2 weeks intra-treatment (n = 48) and 6 weeks post-treatment (n = 61). Primary tumour volumes on MRI at the three time points were calculated and compared for their predictive value for primary site outcome. Volume thresholds optimised to predict failure with the highest accuracy and positive predictive value (PPV) were calculated. The mean pre-treatment volume was 24.6 cm³ (range, 1.1-187.9 cm³) and the mean follow-up interval was 41 months (range, 12-100 months). 23 primary tumours failed treatment (33%). Volumes before, during and after CCRT were positively associated with local failure (p = 0.015, p = 0.009, p<0.0001). Volume reductions during and after CCRT were negatively associated with local failure (p = 0.021, p = 0.001). Pre-treatment and intra-treatment volume thresholds achieved the highest accuracy and produced intermediate PPVs (51-64%) for predicting local failure. Optimised intra-treatment thresholds did not identify any more treatment failures than the pre-treatment thresholds. By comparison, a 6 weeks post-treatment volume reduction (<35%) achieved 100% PPV for failure, albeit with 26% sensitivity. In conclusion, primary tumour volumetry performed early in CCRT provides minimal additional information compared with pre-treatment volumetry, with respect to predicting post-treatment local failures. Therefore, volumetry during CCRT is unlikely to be useful for guiding individual response-based therapeutic modifications.