ObjectivesTo evaluate the safety and efficacy of a 2-weekly cabazitaxel schedule in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and methods ResultsAll patients had received prior docetaxel and 79.1% abiraterone acetate. At inclusion, 46.5% were aged >70 years and 27.9% had an Eastern Cooperative Oncology Group performance status ≥2. Six patients stopped treatment because of toxicity. Grade ≥3 toxicities were: asthenia (16.3%); neutropenia (11.6%); thrombocytopenia (9.3%); diarrhoea (7%), anaemia (4.7%), febrile neutropenia (4.7%) and haematuria (2.3%). In all, 52.4% achieved a ≥30% PSA response and 40.5% had a ≥50% PSA response. The median OS was 15.2 months. ConclusionThis prospective pilot study suggests that cabazitaxel 16 mg/ m² given 2-weekly has a manageable toxicity profile in docetaxel-and abiraterone acetate-pretreated patients with mCRPC. A prospective phase III trial comparing this regimen with the standard cabazitaxel regimen is planned to confirm these results.

Cabazitaxel (25 mg/m2 every 3 weeks) is the standard second-line chemotherapy for patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. It is associated with a risk of neutropenic complications, which may be a barrier to its use in daily clinical practice, particularly in frail elderly patients. Here the authors reviewed key studies conducted with cabazitaxel (TROPIC, PROSELICA, AFFINITY, CARD and the European compassionate use program) and pilot studies with adapted schedules. Based on this review, the use of prophylactic granulocyte colony-stimulating factor from cycle 1 appears crucial to maximize the benefit-risk ratio of cabazitaxel in metastatic castration-resistant prostate cancer. Preliminary data with alternative schedules look promising, especially for frail patients. Results of the ongoing Phase III CABASTY trial (ClinicalTrials.gov: NCT02961257 ) are awaited.

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284 Background: Cabazitaxel (C) administered on a 3-weekly dose schedule has shown a survival benefit in mCRPC patients (pts) pre-treated with docetaxel (D) with concerns about toxicity. We sought to evaluate safety and efficacy of a 2-weekly C schedule. Methods: At the EGP hospital from November 2013 to September 2014, 26 mCRPC pts for whom C was indicated (previously treated with D) received C 16 mg/m² on days 1 and 15 of a 4 weeks-cycle plus daily 10 mg prednisone, until completion of 6 cycles, disease progression, unacceptable toxicity or death. We analyzed safety with toxicity grade ≥ 3 and efficacy, including PSA response, time to biochemical progression (TTBP), radiological progression-free survival (rPFS) and overall survival (OS). Results: 26 pts received C in a 2-weekly schedule; full data are available for 20 pts. Median age was 66.5 years, 34.6% of pts were >70 years; 30.8% had ECOG PS 2; 47.8% had Gleason ≥ 8; 53.8% had lymph node metastases; 96.2% had bone metastases; none had lung or liver metastases. Median D cycles previously received were 6; respectively 80% and 88.4% of pts had received ≥ 2 hormonal manipulations and abiraterone acetate (AA). Median baseline hemoglobin was 12.2 g/dL, median PSA 104.6 ng/mL; 42.9% of pts had ALP ≥ 1.5N, 33.3% had LDH ≥ 1.5N. 4 pts (15%) had grade 1 thrombocytopenia at baseline, 1 (3.8%) had grade 4, reflecting diffuse bone marrow involvement. All pts received G-CSF in primary prophylaxis. Median number of C administration was 7, only 4 pts stopped C because of toxicity (2 for asthenia, 1 for febrile neutroepnia, 1 for thrombocytopenia). Toxicities grade ≥3 were: anemia 33.3%; thrombocytopenia 30%; neutropenia 23.8%; febrile neutropenia 5% (1 pt); no grade ≥3 diarrhea was observed. 45% (9 pts) achieved ≥30% PSA response and 30% (6 pts) ≥50% PSA response. Clinical, biological or radiological response occurred in 50% (10 pts). Median TTBP and rPFS were 3.0 months (2.2-3.6) and 4.2 months (2.8-7.4) respectively. Median OS was not reached at the time of data collection. Conclusions: 2-weekly 16 mg/m² C schedule has a manageable toxicity profile in heavily D and AA pretreated mCRPC pts, and warrants controlled prospective evaluation compared to the standard 3-weekly C schedule.

Background and purpose Few data are available concerning the safety of bevacizumab (B) in combination with locoregional radiation therapy (RT). The objective of this study was to evaluate the 5-year late toxicity of concurrent B and RT in non-metastatic breast cancer. Materials and methods This multicentre prospective study included non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT versus RT alone. All patients received neoadjuvant or adjuvant chemotherapy and normofractionated breast or chest wall RT, with or without regional lymph node RT. B was administered at an equivalent dose of 5 mg/kg once a week for 1 year. The safety profile was evaluated 1, 3 and 5 years after completion of radiotherapy. Results A total of 64 patients were included between November 2007 and April 2010. Median follow-up was 60 months (12–73) and 5-year late toxicity data were available for 46 patients. The majority of tumours were triple-negative (68.8%), tumour size <2cm (41.3%) with negative nodal status (50.8%). Median total dose of B was 15,000mg and median duration was 11.2 months. No grade ≥3 toxicity was observed. Only 8 patients experienced grade 1–2 toxicities: n = 3 (6.5%) grade 1 lymphedema, n = 2 (4.3%) grade 1 pain, n = 1 (2.2%) grade 2 lymphedema, n = 1 (2.2%) grade 1 fibrosis. Five-year overall survival was 93.8%, disease-free survival was 89% and locoregional recurrence-free survival was 93.1%. Conclusion Concurrent B and locoregional RT are associated with acceptable 5-year toxicity in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed.

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Background and Purpose: Recent phase 3 clinical trials have evaluated the addition of bevacizumab (B) to standard chemotherapy in the treatment of patients with non-metastatic breast cancer. But few data are available about the tolerance of B with locoregional radiation therapy (RT). The objective was to evaluate the 5 years late toxicities of the concurrent B and RT in non-metastatic breast cancer. Material and methods: This is a multicenter prospective study including non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT (BEATRICE, BETH, BEVERLY 1, BERVERLY 2) versus RT alone. All patients received neo-adjuvant or adjuvant chemotherapy and normo-fractionated breast or chest wall RT, with or without regional lymph nodes RT. B was administrated as an equivalent of 5 mg/kg every week for 1 year. The safety profile (using the Common Terminology Criteria for Adverse Events version 3.0) was evaluated at 1, 3 and 5 years after the completion of radiotherapy. Results: From October 2007 to January 2012, 151 patients totally included. Median follow-up was 60 months (36-84) and 5 years late toxicities were available for 104 patients (46 with B and RT, 58 with RT alone). Median age was 51 (22-81). 61% of patients received regional lymph nodes RT. The majority of tumor was triple negative (65.6%), tumor size &lt;2cm (50%) and nodal status negative (63.8%). Median total dose of B was 15000 mg (13200 – 18550) and median duration was 11.2 months (11-12.6). No grade ≥3 toxicity was observed. Only 16 patients had grade 1-2 toxicities (8 treated with B and RT, 8 with RT alone): n=4 (3.8%) had grade 1 pain, n=5 (4.8%) had grade 1-2 fibrosis, n=1 (1%) had grade 2 telangiectasia and n=5 (4.8%) had grade 1-2 lymphoedema. No significant difference between the 2 arms was observed. One patient of 46 evaluated had Left Ventricular Ejection Fraction inferior to 50%. At 5 years, overall survival was 93.8%, disease free-survival 89% and locoregional free-survival 93.1 %. Conclusion: Concurrent B and locoregional RT provides acceptable 5-years toxicities in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed. Citation Format: Clément-Zhao A, Tanguy M-L, Cottu P, De La Lande B, Bontemps P, Lemanski C, Baumann P, Levy C, Peignaux K, Reynaud-Bougnoux A, Gobillion A, Kirova Y. TOxicities of Locoregional Radiotherapy Associated with Bevacizumab in patients with non-metastatic breast cancer (TOLERAB): Final long-term evaluation [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 P3-12-06.