METHODS: In the TROIKA trial, patients with ERBB2-positive early breast cancer were randomized and treated with either HD201 or the referent trastuzumab. Eligible patients received 8 cycles of either HD201 or referent trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) every 3 weeks in combination with 8 cycles of chemotherapy (4 cycles of docetaxel, 75 mg/m2, followed by 4 cycles of epirubicin, 75 mg/m2, and cyclophosphamide, 500 mg/m2) in the neoadjuvant setting. The patients then underwent surgery followed by 10 cycles of adjuvant HD201 or referent trastuzumab according to their initial randomization to complete one year of trastuzumab-directed therapy. Event-free and overall survival rates were calculated using Kaplan-Meier analysis. The hazard ratio for event-free survival was estimated by Cox proportional hazards regression.
RESULTS: The final analysis was performed after all patients completed the study at a median follow-up of 37.7 months (Q1-Q3, 37.3-38.1 months). A total of 502 randomized patients received either HD201 or the referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. In this population, the 3-year event-free survival rates were 85.6% (95% CI: 80.28-89.52) and 84.9% (95% CI: 79.54-88.88) in the HD201 and referent trastuzumab groups, respectively (log rank p = 0.938) (HR 1.02, 95% CI: 0.63-1.63; p = 0.945). The 3-year overall survival rates were comparable between the HD201 (95.6%; 95% CI: 91.90-97.59) and referent trastuzumab treatment groups (96.0%, 95% CI: 92.45-97.90) (log rank p = 0.606). During the posttreatment follow-up period, adverse events were reported for 64 (27.4%) and 72 (29.8%) patients in the HD201 and the reference trastuzumab groups, respectively. Serious adverse events were rare and none of which were related to the study treatment.
CONCLUSIONS: This final analysis of the TROIKA trial further confirms the comparable efficacy and safety of HD201 and trastuzumab.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03013504.
OBJECTIVE: To compare the efficacy of HD201 with referent trastuzumab.
DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial (TROIKA) included 502 women with ERBB2-positive early breast cancer treated with either HD201 or referent trastuzumab. It was conducted across 70 centers in 12 countries, including Western and Eastern Europe and Asian countries. Randomization was stratified by tumor hormone receptor status, clinical stage, and geographic region of recruitment. This analysis was conducted on February 12, 2021, after the completion of the adjuvant phase at a median of 31 months (IQR, 28-33 months) of follow-up.
INTERVENTIONS: Patients with ERBB2-positive early breast cancer were randomly assigned to receive HD201 or referent trastuzumab in the neoadjuvant setting for 8 cycles, concurrently with 4 cycles of docetaxel, which was followed by 4 cycles of epirubicin and cyclophosphamide. Patients then underwent surgery, which was followed by treatment with 10 cycles of adjuvant HD201 or referent trastuzumab.
MAIN OUTCOME AND MEASURES: The primary end point was the total pathological complete response (tpCR) assessed after neoadjuvant treatment. Equivalence was concluded if the 95% CI of the absolute difference in tpCR between arms in the per-protocol set was within the margin of more or less than 15%. Other objectives included the breast pathological complete response, overall response, event-free and overall survival, safety, pharmacokinetics, and immunogenicity.
RESULTS: A total of 502 female patients (mean [range] age, 53 [26-82] years) were randomized to receive either HD201 or referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. The baseline characteristics were well balanced between the 2 arms; 195 tumors (38.8%) were hormone receptor-negative , and 213 patients (42.4%) had clinical stage III disease. The tpCR rates were 45% and 48.7% for HD201 and referent trastuzumab, respectively. The difference between the 2 groups was not significant at -3.8% (95% CI, -12.8% to 5.4%) and fell within the predefined equivalence margins. The ratio of the tpCR rates between the 2 arms was 0.92 (95% CI, 0.76 to 1.12). A total of 433 patients (86.1%) presented with 2232 treatment-emergent adverse events of special interest for trastuzumab during the entire treatment period, with 220 (88.0%) and 213 (84.5%) patients in the HD201 and referent trastuzumab groups, respectively.
CONCLUSIONS AND RELEVANCE: The results of this randomized clinical trial found that HD201 demonstrated equivalence to referent trastuzumab in terms of efficacy for the end point of tpCR, with a similar safety profile.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03013504.
METHODS: This retrospective study covered all NPC patients who underwent radical IMRT treatment at the Penang General Hospital from June 2011 to February 2012. Patients of any age and stage of disease with histologically proven diagnosis were included. Information was collected on patient demographics, clinical stage, treatment received, including any neoadjuvant and/or concurrent chemotherapy, acute toxity and completion of IMRT within the OTT.
RESULTS: A total of 26 NPC patients were treated with IMRT during the study period; 88.5% had stage III/IV disease. 45.2% received neo-adjuvant chemotherapy while 50.0% were given concurrent chemo-irradiation. All patients completed the treatment and 92.3% within the 7 weeks OTT. Xerostomia was present in all patients with 92.3% having grade 2. Severe grade III/IV acute toxicity occurred in 73.1% of patients, the commonest of which was oral mucositis (57.6%). This was followed by dysphagia which occurred in 53.8%, skin reactions in 42.3% and weight loss in 19.2%. However, haematological toxicity was mild with only one patient having leucopaenia.
CONCLUSION: IMRT treatment for NPC is feasible in our center. More importantly, it can be delivered within the 7 weeks OTT in the majority of patients. Severe grade 3/4 toxicity is very common (73.1%) and thus maximal nutritional and analgesic support is required throughout the treatment.
MATERIALS AND METHODS: This retrospective study examined NPC patients between 1st January 2001 and 31st December 2005 in Penang General Hospital. Survival analyses were performed using the Kaplan-Meier method and comparisons between groups were made using the log-rank test. Important prognostic factors including patient demographics, tumour and treatment factors were analysed using the Cox proportional hazard model.
RESULTS: A total of 285 patients were identified with a median age of 51 years, 72.6% being males. The majority were Chinese (66%) followed by Malays (31.9%). Primary tumour stages (T stages) 3 and 4 were present in 18.6% and 34% of patients respectively, and nodal disease was present in 80.4%. On overall AJCC staging, 29.1% had stage III and 50.2% had stage IV disease. Some 39.6% of patients had WHO type 3 histology and 7.4% had WHO type 1-2 histology with the remainder having NPC with no subtype reported. Concurrent chemo-irradiation was the commonest treatment received by patients (51.9%) followed by radiotherapy alone (41.8%). The 5 year overall survival and cause specific survival were 33.3% and 42.7% respectively. Age group, T stage, N stage and WHO histological subtype were independent prognostic factors for overall survival on multivariate analysis. For cause specific survival they were T stage and N stage.
CONCLUSION: The 5 years overall survival rate was 33.3%. This low figure is primarily due to late presentation. Efforts to detect NPC at earlier stages in Malaysia are urgently needed. These should include public education to increase awareness of the prevalence of this highly treatable disease.
METHODS: We designed a questionnaire, including 50 questions related to debulking surgery for advanced ovarian cancer. The questionnaire was sent to Gynecologic Oncologic Groups in Asia from December 2016 to February 2017.
RESULTS: A total of 253 gynecologic oncologists from Japan (58.9%), the Republic of Korea (19%), Taiwan (12.6%), and the other counties including China (7.5%), Malaysia (0.8%), Indonesia (0.8%), and Thailand (0.4%) participated in this E-survey. The median number of debulking surgeries per year was 20, and 46.8% of the respondents preferred <1 cm as the criterion for optimal debulking surgery (ODS). The most common barrier and surgical finding precluding ODS were performance status (74.3%) and disease involving the porta hepatis (71.5%). Moreover, 63.2% had a fellowship program, and only 15% or less had opportunities to receive additional training courses in general, thoracic, or urologic surgery. The median percentage of patients receiving neoadjuvant chemotherapy (NAC) was 30%, and the achieved rate of ODS in primary debulking surgery (PDS) and interval debulking surgery (IDS) was 65% and 80%, respectively. Most of the respondents required three to 6 h for PDS (48.6%) and IDS (58.9%). Moreover, more than 50% depended on ultra-radical surgery conducted by specialists.
CONCLUSIONS: The ODS criteria are relatively lenient with a preference for NAC in 30% of the respondents in Asia. This trend might be associated with the dependence on aggressive surgery performed by specialists.
Case presentation: We present a case of 15-year-old boy from rural area, presented with chronic diarrhea and per rectal bleeding for 3 months. The diagnosis was determined by colonoscope which revealed a fungating mass identified at 10cm from anal verge. Histological examination confirmed diagnosis of signet ring cell adenocarcinoma. CT scan of the abdomen showed thickening involving the recto-sigmoid colon and rectal mass, without evidence of distant metastatic disease. The patient's carcinoembryonic antigen level was within the normal range. He underwent a colostomy and was subjected to neoadjuvant CCRT and surgery.
Discussion: This CASE highlights the importance and challenges in achieving early diagnosis and surgical intervention of signet-ring cell carcinoma in adolescents, as most cases are detected at an advanced stage coupled with the scarcity of information on these rarer subtypes which leads to a poor prognosis.
Conclusion: In managing Signet cell carcinoma of the colorectal, physician have to know that it has a poor prognosis in patients of any age. However, in young teenagers delayed diagnosis and treatment option are narrowed to palliative management. Genetic profiling of family members and similar environment population may be a key to early detection.
Methods: 80 patients with invasive breast cancer receiving BCS after neoadjuvant chemotherapy were included in this non-randomized case-control study. 40 patients with specimen radiography performed in a standard approach (control group) were compared to 40 patients with use of a radiopaque tissue transfer system (study group).
Results: 19/80 (23.75%) patients required re-excision because of involved margins; among those, 14/40 (35%) were in the control group and 5/40 (12.5%) in the study group. The association between the use of the radiopaque tissue transfer system and the lower re-excision rate was statistically significant (p = 0.023).
Conclusion: Our analysis provides a rationale for the routine use of a radiopaque tissue transfer system for specimen radiography in BCS after neoadjuvant chemotherapy for invasive breast cancer in order to reduce re-excision rates.
METHODS: Surgeons in the APFCP completed an Institutional Review Board-approved anonymous e-survey and/or printed letters (for China) containing 19 questions regarding nonsurgical close observation in patients who achieved clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT).
RESULTS: Of the 417 responses, 80.8% (n = 337) supported the W&W approach and 65.5% (n = 273) treated patients who achieved cCR after nCRT. Importantly, 78% of participants (n = 326) preferred a selective W&W approach in patients with old age and medical comorbidities who achieved cCR. In regard to restaging methods after nCRT, the majority of respondents based their decision to use W&W on a combination of magnetic resonance imaging results (94.5%, n = 394) with other test results. For interval between nCRT completion and tumor response assessment, most participants used 8 weeks (n = 154, 36.9%), followed by 6 weeks (n = 127, 30.5%) and 4 weeks (n = 102, 24.5%). In response to the question of how often responders followed-up after W&W, the predominant period was every 3 months (209 participants, 50.1%) followed by every 2 months (75 participants, 18.0%). If local regrowth was found during follow-up, most participants (79.9%, n = 333) recommended radical surgery as an initial management.
CONCLUSION: The W&W approach is supported by 80% of Asia-Pacific surgeons and is practiced at 65%, although heterogeneous hospital or society protocols are also observed. These results inform oncologists of future clinical study participation.