A vascular endothelial growth factor (VEGF) inhibitor might enhance metronomic chemotherapy in previously treated metastatic breast cancer (MBC) patients. Anthracycline and taxane refractory MBC patients were given cyclophosphamide 50 mg p.o. daily, methotrexate 1 mg/kg i.v. every 14 days, and bevacizumab 10 mg/kg i.v. every 14 days. Trastuzumab was added in HER2-overexpressing tumors. 24 patients were enrolled and 22 were evaluable. All tumors had histologic grade II-III and most patients had > or =2 metastatic sites. After a median follow-up of 7.7 months the response rates were: complete response (CR) 0%, partial response (PR) 31.8% (95% CI 13.9- 54.9%), stable disease for >or =24 weeks (SD) 31.8% (95% CI 13.9-54.9%). Clinical benefit (CB= CR + PR + SD>24w) 63.6% (95% CI 40.7-82.8%). Median progression-free survival (PFS) was 7.5 months; overall survival (OS) was 13.6 months. HER2-overexpressing or high proliferative-index tumors had better 6-month PFS (75% vs. 34% in HER-negative tumors, P = 0.043; 67% vs. 0% in Ki-67 > or =20% tumors, P = 0.015). Adverse effects were mild. The combination of bevacizumab and a metronomic-based chemotherapy was effective, well tolerated and provided clinical benefit in heavilytreated MBC patients.

BackgroundCirculating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to estimate the prognostic value of the dynamic quantification of ctDNA levels.Materials and MethodsA total of 251 serial plasma samples from 41 non-small-cell lung cancer patients who carried an activating EGFR mutation were analysed by digital PCR. For survival analysis, ctDNA levels were computed as a time-dependent covariate.ResultsDynamic ctDNA measurements had prognostic significance (hazard ratio for overall survival and progression free survival according to p.T790M mutant allele frequency; 2.676 and 2.71 respectively; P < 0.05). In the same way, patients with p.T790M-negative or unchanging or decreasing plasma levels of sensitizing EGFR mutation were 12 and 4.8 times more likely to maintain response or stable disease, respectively, than patients in which the opposite occurred (P < 0.05).On average, the p.T790M mutation was detected in plasma 51 days before the assessment of progression disease by CT-scan. Finally, ctDNA outperformed CTCs for assessing tumor progression (P = 0.021).ConclusionsThe appearance or increase in a unit of the p.T790M allele frequency almost triples the risk of death and progression. This information can be used to design clinical trials aiming to estimate whether T790M positive patients should start second line treatment based on molecular data rather than imaging data.

Background: Survival data support the use of first-line osimertinib as the standard of care for epidermal growth factor receptor (EGFR)epositive non-small cell lung cancer (NSCLC). However, it remains unclear whether upfront osimertinib is superior to sequential first-or second-generation tyrosine kinase inhibitors (TKIs) followed by osimertinib for all patients. It is impossible to predict which patients are at high risk of progression, and this constitutes a major limitation of the sequential TKI approach. Patients and methods: A total of 830 plasma samples from 228 patients with stage IV, EGFRpositive NSCLC who were treated with first-line TKIs were analysed by digital polymerase chain reaction (dPCR). Results: The circulating tumour DNA (ctDNA) levels helped to identify patients with significantly improved survival rate, regardless of the treatment. Patients treated with first-or second-generation TKIs (N Z 189) with EGFR mutations in plasma at a mutant allele frequency (MAF) <7% before treatment initiation (low-risk patients) or who were ctDNA negative after 3 or 6 months of treatment and with an MAF <7% at diagnosis (high responders) had two-thirds lower risk of death than patients in the opposite situation (adjusted hazard ratio [HR] Z 0.38; 95% confidence interval [CI]: 0.23e0.64 and HR Z 0.22; 95% CI: 0.12e0.42, respectively). The median overall survival (OS) for low-risk patients and high responders treated with first-or second-generation TKIs was 34.2 months and not reached, respectively, regardless of second-line treatment. There were no significant difference in OS between lowrisk or high-responder patients treated upfront with osimertinib (N Z 39) and those treated under a sequential approach with osimertinib (N Z 60). Median OS was not reached in both cases. Conclusions: Pre-treatment ctDNA levels identify low-risk patients, who may benefit from sequential TKI treatment. Information regarding EGFR mutation clearance can help to improve patient selection.

SBRT is effective and safe. The main failure pattern is distant progression. The selection of patients with a high probability of remaining oligometastatic is crucial for the efficiency of SBRT, both clinically and in terms of resources.

10617 Background: Whether trastuzumab should be continued after tumor progression remains unknown.We describe the activity of successive trastuzumab-containing regimens in patients with HER2-overexpressing metastatic breast cancer, as well as the response rate, time to progression and predictive factors for response. Methods: Descriptive retrospective study of trastuzumab activity in patients with HER2-overexpressing metastatic breast cancer treated at our hospital from 10/1999 to 07/2005. Results: 93 consecutive patients were evaluated obtaining an objective response rate (OR) for first-time administration of trastuzumab of 46.2%; stable disease (SD) 24.7%; clinical benefit (CB) 71%. Median time-to-progression (TTP) was 5 months (range: 1–39+). A total of 47 pts (50.5%) received a second trastuzumab-containing regimen with an OR of 29.8%; SD 21.3%; CB 51.1%; TTP 4 months (range: 1–31). A total of 21 pts (22.6%) received a third trastuzumab-containing regimen; OR 38.1%; SD 23.8%; CB 61.9%; TTP 4 months (range: 1–30+). A total of 10 pts (10.8%) received a fourth trastuzumab-containing regimen; OR 20%; SD 20%; CB 40%; TTP 4 months (range: 1–37). 5 pts (5.4%) received a fifth trastuzumab-containing regimen; OR 0%; SD 60%. Age < 45 years is a significant prognostic factor (p: 0.005, 95% CI, OR 5.6 (1.5–20.6)). A better response rate in the successive trastuzumab-containing regimens was observed, when there was a response in the first regimen: p = 0.04; 95% CI; OR 3.84 (1.07–14.65). With a follow-up of 16,5 months 45 pts (48,4%) are alive. Conclusions: Trastuzumab-containing therapies beyond disease progression in metastatic breast cancer show activity. There were more responses in younger pts. Those pts who had a previous response to trastuzumab therapy were more likely to respond to successive trastuzumab-containing regimens. Additional controlled studies are needed to test this approach. No significant financial relationships to disclose.