Abstract
Rationale: Quality of Life is of prime importance in Advanced Breast Cancer (ABC), a mostly non-curable disease. Both paclitaxel (P) and vinorelbine as single-agent chemotherapy (CT) are ...recommended treatment options in the management of ABC non-responsive to hormone therapy (HT) and with no visceral crisis. These agents are active with a good tolerance profile. The benefits and safety of oral vinorelbine (OV) and weekly P have however never been evaluated in a face to face trial.
Methods: Main eligibility criteria included: age ≥18 years, documented locally recurrent or metastatic involvement previously untreated by CT, estrogen receptor positive disease previously treated by at least one HT, HER2-negative status, Karnofsky PS ≥70 and presence of at least one measurable lesion. Study treatment (until progression): Arm A, OV 80 mg/m2 weekly (following a first cycle at 60 mg/m2 and dose escalation to 80 in the absence of grade 3 or 4 toxicity); Arm B: paclitaxel 80 mg/m2 weekly. One cycle was defined as three weeks of treatment. Patients were stratified according to prior taxane (yes/no) and visceral metastases (yes/no). Primary endpoint was disease control rate (DCR), defined as confirmed complete response/partial response/stable disease of a minimum duration of 6 weeks.
Results: 131 pts have been randomized (OV 66; P 65). Baseline patient characteristics (Arms A/B): median age 58/61 years; median number of previous HT 2/2; prior (neo)adjuvant CT 74/72%; prior anthracycline 64/62%; prior taxane 39/42%; >3 metastatic sites 42/48%; visceral metastases 80/78%. Safety: the most common non-haematological related G3/4 adverse events (≥3% patients) were: fatigue 7.6/1.5%, peripheral neuropathy 0/4.6%, nausea 3/0%, diarrhoea 3/1.5%, vomiting 3/0%, constipation 3/1.5%; alopecia (G2) was present in 1.5/33.8%; no toxic deaths observed. Efficacy: DCR in the intent-to-treat population was 95%CI 75.8 63.6-85.5/75.4 63.1-85.2 %; overall response was 20/40%; stable disease was 56/35% respectively. Treatment exposure, other efficacy / safety parameters and quality of life results will be presented during the meeting.
Conclusion: Both OV and P reached similar DCR rates of 75%. As expected, each regimen presented a specific tolerance profile, with, in particular, a lower incidence of alopecia and peripheral neuropathy with OV.
Citation Format: Aapro M, Ruiz Borrego M, Staroslawska E, Morales S, Cinieri S, De Freitas Junior R, Garcia Estevez L, Szombara E, Hervieu H, Groc M, Villanova G, Hegg R. Randomized phase II study evaluating weekly oral vinorelbine versus weekly paclitaxel in estrogen receptor positive, HER2-negative patients with advanced breast cancer (NorBreast-231 trial) abstract. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-14-03.
Abstract
Background: Single-agent chemotherapy (CT) is the standard treatment option in endocrine receptor (ER)-positive advanced breast cancer (ABC) after failure of endocrine therapy (ET) or in ...patients (pts) without visceral crisis. Both weekly paclitaxel (WP) and oral vinorelbine (OV) are among the recommended treatment options in this setting. The aim of this study was to evaluate the efficacy and safety profiles of OV and WP in a face to face study.
Material and methods: Pts with ER-positive, HER2-negative ABC, with an age ≥18 years and with a documented locally recurrent or metastatic involvement previously untreated by CT were eligible. Pts were randomized to receive, as first-line CT, 3 weekly-cycles of either: ARM A: weekly OV, given as a 80 mg/m2 dose (following a first cycle at 60 mg/m2, dose escalation to 80 in the absence of grade 3 or 4 toxicity at cycle 1); ARM B: WP 80 mg/m2 per week. Primary endpoint was disease control rate (DCR). Pts were stratified according to prior taxane CT and visceral metastases.
Results: 131 pts have been treated (OV: 66, WP: 65). Baseline pts characteristics (Arms OV/WP): median age 58/61 years; median number of prior ET: 2/2; prior (neo) adjuvant CT 74/72%; prior anthracycline 67/62%; prior taxane: 41/42%; >3 metastatic sites 42/48%; visceral metastases 79/79%. Median number of cycles (range): 6(1-55)/7(1-44); dose escalation of OV was performed in 75% of pts. Safety: most common non-hematological related G3/4 adverse events per pt were fatigue 8/2%, peripheral neuropathy 0/5%, nausea 3/0%, diarrhoea 3/2%, vomiting 3/0%, constipation 3/2%, alopecia (G2) 2/34%, no toxic deaths; febrile neutropenia was present in 2/0% of pts. Quality of life: over time, no major differences between both arms have been observed. Efficacy: DCR in the intent-to-treat population was 95%CI 75.8 63.6-85.5 /75.4 63.1-85.2%; overall response rate 20/40%; median progression-free survival: 5.5/6.4 months. Median overall survival was: OV 27.6/WP 22.3 months.
Conclusion: Both OV and WP reached similar DCR rates of 75%. Each regimen presented a specific tolerance profile, with, in particular, a lower incidence of alopecia and peripheral neuropathy with OV. OV and WP are valid first-line CT options for ER-positive/HER2-negative pts with ABC.
Citation Format: Aapro MS, Hegg R, Ruiz Borrego M, Staroslawska E, Morales S, Cinieri S, De Freitas Junior R, Garcia Estevez L, Szombara E, Hervieu H, Groc M, Villanova GR. Final results of NorBreast-231, a randomized phase II study evaluating weekly oral vinorelbine versus weekly paclitaxel as first-line chemotherapy in patients with advanced breast cancer 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 P1-14-01.
F17464 is a new highly potent preferential D3 antagonist, 5-HT1A and weak D2 partial agonist, with confirmed antipsychotic-like activity in animal models. In healthy volunteers, F17464 had a good ...safety and tolerability profile. A PET-scan study determined a high D3 occupancy rate up to 22h after a single dose.
The primary objective was to evaluate the efficacy of 40mg/day of oral F17464 in comparison to placebo.
This double-blind, parallel group, multicenter study included patients with acute exacerbation of schizophrenia treated for 6 weeks as antipsychotic monotherapy. Patients were hospitalised for the first 3 weeks of treatment, then continued as outpatients.
The 144 randomized patients had a baseline PANSS mean (SD) total score was 89.6 (9.5). The change from baseline of PANSS total score to Day 43 on the FAS (LOCF), showed a statistically significant difference in favor of F17464 over placebo: adjusted mean (SE) change −13.5 (2.1) on F17464 and −7.8 (2.2) on placebo with a treatment effect estimate −5.7 (2.7). The 20% or 30% response rate was statistically higher in the F17464 group (47.2% and 25.0%) compared to the placebo group (30.6% and 13.9%). The incidence of treatment-emergent adverse events was slightly higher in the F17464 group (70.8%) than in the placebo group (62.5%). There were no clinically-relevant hepatic, metabolic, or cardiovascular abnormalities. No EPS was reported under F17464.
This is the first D3 antagonist that proves efficacy. The results of this phase 2 study also demonstrate the favorable safety profile of F17674 when compared to placebo.
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