Final Results of the Randomized Phase II NorCap-CA223 Trial Comparing First-Line All-Oral Versus Taxane-Based Chemotherapy for HER2-Negative Metastatic Breast Cancer.

BACKGROUND: The purpose of this study was to evaluate the efficacy of 3 first-line chemotherapy combination regimens for HER2-negative metastatic breast cancer (mBC). PATIENTS AND METHODS: In this open-label, 3-arm, randomized phase II trial, patients were randomized to all-oral NORCAP (vinorelbine/capecitabine), GEMPAC (gemcitabine/paclitaxel), or GEMDOC (gemcitabine/docetaxel) as first-line chemotherapy for HER2-negative mBC. Stratification factors were center, previous (neo)adjuvant anthracycline, and age. The primary end point was disease control rate (DCR; complete or partial response, or stable disease for ≥3 months). RESULTS: The DCR was 73% (95% confidence interval [CI], 59-85) with NORCAP (36 of 49 patients), 78% (95% CI, 64-88) with GEMPAC (39 of 50 patients), and 80% (95% CI, 66-90) with GEMDOC (40 of 50 patients). Objective response rates were 33% (16 of 49 patients), 24% (12 of 50 patients), and 50% (25 of 50 patients), respectively; median progression-free survival was 7.6, 9.0, and 11.4 months, respectively. Median overall survival was 30 to 31 months with all regimens. The most common Grade ≥3 adverse event with each regimen was neutropenia (24 patients [50%], 23 patients [46%], and 43 patients [86%], respectively). The most common nonhematological Grade ≥3 adverse event was fatigue. Grade 2 alopecia occurred in 36 patients (72%) who received GEMPAC and 38 patients (76%) who received GEMDOC, but only 4 patients (8%) who received NORCAP. There was no evidence of a detrimental effect of NORCAP on quality of life. CONCLUSION: All-oral NORCAP is an active first-line chemotherapy regimen and might be offered as an alternative to first-line taxane-based therapy for HER2-negative mBC, particularly if patients wish to avoid alopecia or frequent intravenous administrations.

Geriatric screening results and the association with severe treatment toxicity after the first cycle of (radio)chemotherapy.

BACKGROUND: Screening tools are used in geriatric oncology to determine who should receive a Comprehensive Geriatric Assessment (CGA). However, in this prospective study, we evaluated the association between geriatric screening results, measured with the G8 and Groningen Frailty Indicator (GFI), and severe treatment toxicity. METHODS: Patients over 65 years with various types and stages of cancer were screened with the G8 and the GFI prior to the start of treatment. The association between geriatric screening results and Serious Adverse Events (SAE) after the first cycle of (radio)chemotherapy were studied with bivariate analysis (normal versus abnormal screening test) and logistic regression analysis. RESULTS: From 170 screened patients, 85 patients were eligible for this study. The median age was 76 years (range: 66-88 years). The treatment intent was curative in 46% and palliative in 54%. A SAE occurred in 15 patients (18%) of which three resulted in death. There was no significant association between the G8, as a dichotomous predictor (p = 0.376) or as a continuous predictor (p = 0.298), and risk of a SAE. We also found no significant association for the GFI analysed as a dichotomous predictor (cut-off ≥4: p = 0.384; cut-off ≥3: p = 0.773), nor as a continuous predictor (p = 0.734). All associations remained insignificant when adjusted for treatment type and comorbidity. CONCLUSION: The G8 and the GFI can be used to select patients for CGA, but they do not seem to be predictive for short-term severe treatment toxicity.

Evaluation of the Groningen Frailty Indicator and the G8 questionnaire as screening tools for frailty in older patients with cancer.

OBJECTIVE: In this study, we evaluated the Groningen Frailty Indicator (GFI) and the G8 questionnaire as screening tools for a Comprehensive Geriatric Assessment (CGA) in older patients with cancer. PATIENTS AND METHODS: Eligible patients with various types and stages of cancer were evaluated for frailty before treatment. Patients were categorized as patients with a normal CGA and abnormal CGA (≥2 impaired tests). The diagnostic performance of the screening tools was evaluated against the CGA with Receiver Operating Characteristic analysis. RESULTS: In total, 170 patients (79 women) with median age 77years old (range 66-97years) were included. Sixty-four percent of patients had an abnormal CGA while according to the GFI (GFI≥4) and G8 questionnaire (G8≤14) 47% and 76% of patients had an abnormal screening test, respectively. Overall, there was no significant difference (p=0.97) in diagnostic performance between the two screening tools. The Area Under the Curve was 0.87 for both tools. For the GFI and G8 questionnaire the sensitivity was respectively 66% (95% CI: 56-75%), 92% (95% CI: 85-96%); the negative predictive value (NPV): 59% (95 CI%: 49-69%), 78% (95% CI: 63-88%); and the specificity: 87% (95% CI: 76-94%), 52% (95% CI: 39-65%). CONCLUSION: In this study, we showed that overall both the GFI and the G8 questionnaire were able to separate older patients with cancer with a normal and abnormal CGA. For the G8 questionnaire, an adequate sensitivity and NPV were demonstrated, however at the expense of the specificity. For the GFI, we suggest to lower the threshold with one point to GFI ≥3 to screen patients for a CGA.

Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia.

PURPOSE: The concomitant use of intravenous (IV) iron as a supplement to erythropoiesis-stimulating agents in patients with chemotherapy-induced anemia is controversial. This study was designed to evaluate the efficacy and safety of darbepoetin alpha given with IV iron versus with local standard practice (oral iron or no iron). PATIENTS AND METHODS: In this multicenter, randomized, open-label, phase III study, 396 patients with nonmyeloid malignancies and hemoglobin (Hb) less than 11 g/dL received darbepoetin alpha 500 microg with (n = 200) or without (n = 196) IV iron once every 3 weeks (Q3W) for 16 weeks. RESULTS: The hematopoietic response rate (proportion of patients achieving Hb >or= 12 g/dL or Hb increase of >or= 2 g/dL from baseline) was significantly higher in the IV iron group: 86% versus 73% in the standard practice group (difference of 13% [95% CI, 3% to 23%]; P = .011). Fewer RBC transfusions (week 5 to the end of the treatment period) occurred in the IV iron group: 9% versus 20% in the standard practice group (difference of -11% [95% CI, -18% to -3%]; P = .005). Both treatments were well tolerated with no notable differences in adverse events. Serious adverse events related to iron occurred in 3% of patients in the IV iron group and were mostly gastrointestinal in nature. CONCLUSION: Addition of IV iron to darbepoetin alpha Q3W in patients with chemotherapy-induced anemia was well tolerated, resulting in an improved hematopoietic response rate and lower incidence of transfusions compared with darbepoetin alpha alone.