Trastuzumab without chemotherapy in the adjuvant treatment of breast cancer: subgroup results from a large observational study.

BACKGROUND: The topic of trastuzumab therapy without chemotherapy in early breast cancer (EBC) has been repeatedly discussed at international consensus meetings, but is compromised by the lack of solid evidence from clinical studies. METHODS: An observational study database of patients with EBC receiving trastuzumab-containing (neo)adjuvant therapy was screened to identify those patients who did not receive cytostatic agents. RESULTS: Of 3935 patients, 232 (6%) were identified who received no chemotherapy, being characterized by older age, worse performance status, and/or less aggressive histology. Relapse-free survival in this cohort was 84% (95% confidence interval [CI] 78-89%) at 3 years and 80% (95% CI 74-87%) at 5 years. However, these rates were significantly worse than those in the group of patients who received chemotherapy (hazard ratio 1.49; 95% CI 1.06-2.09; P = 0.022). A similar pattern was observed for overall survival, with marginally non-significant inferiority in the group receiving no chemotherapy (hazard ratio 1.56; 95% CI 1.00-2.44; P = 0.052). Survival rates in patients receiving no chemotherapy were 93% (95% CI 88-97%) and 87% (95% CI 81-93%) at 3 and 5 years, respectively. These findings were confirmed by a propensity score analysis accounting for selection bias. CONCLUSIONS: Trastuzumab plus chemotherapy should remain the preferred option in all patients with HER2-positive EBC with an indication for adjuvant treatment. However, a limited proportion of patients will need an alternative treatment approach, either because of contraindications or the patient's preference. In these selected patients, trastuzumab monotherapy, eventually combined with endocrine agents, might be a reasonable option offering favorable long-term outcomes by addressing the high-risk profile associated with HER2-positive disease.

Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Results of a Prospective, Noninterventional Study on Routine Treatment Between 2006 and 2012 in Germany.

PURPOSE: Trastuzumab is part of the standard treatment in patients with human epidermal growth factor receptor 2-positive early breast cancer in addition to (neo)adjuvant chemotherapy. This German prospective noninterventional study, which included major patient cohorts underrepresented in the pivotal randomized studies, examined the generalizability of the results of those studies. PATIENTS AND METHODS: Between 2006 and 2012, 4,027 patients were enrolled and treated with trastuzumab; they were unselected regarding age or concomitant/sequential adjuvant chemotherapy. Long-term outcome data were obtained in yearly intervals. All analyses were descriptive in nature. RESULTS: Among 3,940 evaluable patients, 26% were elderly (older than 65 years of age). More than half of the population had pN0 tumor stage. Ninety-four percent received chemotherapy: 78% as adjuvant treatment and 14% as neoadjuvant treatment, 2% both. Anthracyclines were administered in 87% and taxanes in 66%. Trastuzumab was stopped prematurely in 9% (because of cardiotoxicity in 3.5%). Recurrence-free survival was 90.0% (95% confidence interval [CI], 88.9%-91.1%) and 82.8% (95% CI, 81.2%-84.4%) after 3 and 5 years, respectively. The corresponding figures for overall survival were 96.8% (95% CI, 96.1%-97.6%) and 90.0% (95% CI, 88.6%-91.4%). Pathological primary tumor size, lymph node involvement, and hormone receptor status had the greatest independent effect on recurrence risk. Cardiac function toxicity of National Cancer Institute common toxicity criteria grade ≥2 and ≥3 was observed in 2.5% and less than 1% of patients, respectively. CONCLUSION: The maturing follow-up data seem to confirm the beneficial results of trastuzumab treatment for early breast cancer from the randomized studies. Moreover, these findings support use of trastuzumab-based therapy in patients groups less commonly included in the phase III trials (e.g., elderly patients and those with stage I disease). The Oncologist 2017;22:131-138Implications for Practice: On the basis of the results of large pivotal phase III studies, the inclusion of trastuzumab in adjuvant treatment regimens for human epidermal growth factor receptor 2-positive breast cancer is standard of care. However, in these trials, elderly patients, those with comorbidities, and/or those with contraindications or refusal of cytotoxic chemotherapy are typically underrepresented. This study provides data on observed treatment options, outcomes, and risks in a wider, unselected patient population (including more than 1,000 patients with stage I disease), treated routinely in several institutions of varying size and location across Germany.

Phase III study on efficacy of taxanes plus bevacizumab with or without capecitabine as first-line chemotherapy in metastatic breast cancer.

Taxanes (T) plus bevacizumab (B) and taxanes plus capecitabine (X) showed better progression-free survival (PFS) compared to taxanes alone. Since life-threatening or highly symptomatic situations require polychemotherapy in metastatic breast cancer (MBC), combination of taxanes, capecitabine plus bevacizumab appears reasonable. TABEA (NCT01200212), a prospectively randomized, open-label, phase III trial compares taxanes (paclitaxel 80 mg/m(2) i.v. d1,8,15 q22 or docetaxel 75 mg/m(2) i.v. d1 q22) plus bevacizumab (15 mg/kg i.v. d1 q22) with (TBX) or without capecitabine (TB, 1800 mg/m(2) daily d1-14 q22) as first-line therapy in MBC. Histologically confirmed HER2-negative, locally advanced or MBC patients with a chemotherapy indication and measurable or non-measurable target lesions (RECIST criteria) were included. Primary objective was PFS. Secondary objectives were response rate and duration, clinical benefit rate (complete response, partial response, stable disease ≥24 weeks), 3-year overall survival, PFS in patients ≥65 years, toxicity, and compliance. We assumed 10 and 13.3 months PFS for TB and TBX, respectively (HR = 0.75), requiring 432 patients and 386 events. Preplanned interim futility and safety analyses after 100 events in 202 patients showed no efficacy benefit and higher toxicity for TBX. Recruitment and therapy were stopped following advice from the IDMC. Final analysis revealed a HR 1.13 [95 %CI 0.806-1.59], P = 0.474, for PFS. Overall grade 3-4 adverse event (77.3 vs. 62.1 %, P = 0.014) and serious adverse event (40.0 vs. 30.2 %, P = 0.127) rates were higher for TBX after 26.1 months median follow-up, with six deaths for TBX versus 1 for TB. Adding capecitabine to TB cannot be recommended as first-line therapy in MBC.

Total mesometrial resection (TMMR) for cervical cancer FIGO IB-IIA: first results from the multicentric TMMR register study.

OBJECTIVE: The surgical concept of total mesometrial resection (TMMR) and therapeutic lymphadenectomy (tLNE) for the treatment of early cervical cancer is based on the ontogenetic cancer field model. Unicentric data show excellent locoregional control rates without adjuvant chemoradiation. However, there are so far no prospective, multicentric data supporting the method. METHODS: The multicentric TMMR register study was designed to answer the question whether the concept of TMMR+tLNE could be transferred to different centers and surgeons without compromising the outstanding oncologic results described in a unicentric setting. RESULTS: In 116 patients with cervical cancer stages IB-IIA, (International Federation of Gynecology and Obstetrics [FIGO] 2018), who underwent TMMR/tLNE, 25.0% were lymph node-positive. pT stages were pT1a in 3 patients (2.6%), pT1b1 in 82 (70.7%), pT1b2 in 18 (15.5%), pT2a in 4 (3.5%) and pT2b in 9 (7.8%). The overall recurrence rate was 7.8% in a median follow-up time of 24 months (6-80). Locoregional recurrences occurred in 6.0% of patients. One patient (0.9%) died from the disease during the observation period. CONCLUSION: These are the first multicentric data on the surgical concept of TMMR and tLNE for the treatment of cervical cancer FIGO IB-IIA. We were able to reproduce the excellent oncologic data described for the method albeit with a relatively short median observation time. A randomized controlled trial seems warranted to definitely establish TMMR+tLNE as the method of choice for the treatment of early cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01819077.

Trastuzumab in the treatment of elderly patients with early breast cancer: Results from an observational study in Germany.

BACKGROUND: In elderly patients with HER2-positive breast cancer, few data on efficacy and toxicity of adjuvant trastuzumab treatment exists since older patients were in general excluded from large randomized studies. This prospective observational study aimed to confirm the beneficial findings from pivotal trials in age cohorts ≥65 years. MATERIALS AND METHODS: There were no restrictions for recruitment with respect to age or concomitant/sequential adjuvant medication. Long-term relapse/survival status of the patients was assessed once a year. RESULTS: Among the 3940 evaluable patients enrolled between 2006 and 2012 at 339 institutions, 507 were aged between 65 and 69 years, with another 507 patients ≥70 years. Elderly patients suffered from significantly more advanced primary tumors. Preceding or concomitant chemotherapy showed decreasing aggressiveness with patient's age. Trastuzumab treatment was stopped prematurely in only 11% of the elderly, but more often than in younger patients (p=0.0008). With 453 events hitherto reported, elderly patients did not exhibit an inferior relapse-free survival when adjusted for other relevant prognostic factors (hazard ratio: 1.01 per year; p=0.24). Three-year overall survival was significantly lower in the population older than 64 years than in younger patients (94.2% vs. 96.8%, p=0.0011). CONCLUSIONS: To our knowledge, our population of elderly patients treated with adjuvant trastuzumab is the largest analyzed so far. The beneficial long-term results were comparable to those in the younger cohorts. Although the risk of cardiotoxicity increased significantly with age, it also remained manageable in older patients. Thus, chronological age alone should not preclude HER2 antibody treatment.