Real world initial palliative treatment patterns and clinical outcomes in premenopausal patients with hormone receptor-positive,HER2-negative metastatic breast cancer: A study of the National Cancer Center,China

BackgroundTo observe whether guideline non-adherence in initial palliative treatment choices for premenopausal hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) patients result in worse clinical outcomes in the Chinese population.MethodsThe China National Cancer Center database was used to identify 2194 patients diagnosed between 2004 and 2015. A total of 451 premenopausal patients with HR + HER2- MBC were included. Clinicopathological features and survival information were extracted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using log-rank test.ResultsThe number of patients receiving initial chemotherapy, endocrine therapy and chemo-endocrine therapy were 222 (49.2%), 80 (17.7%), and 149 (33.0%), respectively. Patients receiving initial chemotherapy were more likely to be luminal B subtype, had more de novo stage IV disease and more liver metastasis, compared with patients receiving initial endocrine therapy. Both PFS and OS were significantly longer for chemo-endocrine therapy group (median PFS 18.9 months and OS 75.0 months), than for endocrine therapy group (median PFS 11.7 months and OS 53.5 months), and chemotherapy group (median PFS 7.1 months and OS 43.9 months). In multivariate analysis, none of the three treatment strategies were independently associated with PFS or OS.ConclusionIn real world, a high percentage of premenopausal patients with HR + HER2- disease received chemotherapy as initial palliative treatment in China, which was not associated with worsened survival. Further studies with larger sample size across China are needed to explore the relationship between this guideline non-adherence and clinical outcomes.     

Outcomes of patients with metastatic renal cell carcinoma with sarcomatoid dedifferentiation to immune checkpoint inhibitors

IntroductionMetastatic renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is associated with poor survival outcomes. We aimed to analyze the efficacy and safety of immune checkpoint inhibitors (ICI) in patients with sRCC comparing clear-cell (sccRCC) to non-clear cell epithelial histology (snccRCC).MethodsWe performed retrospective analysis of sRCC patients who received ICI at MD Anderson Cancer Center (n = 48, 41 with ccRCC and 7 with nccRCC) to determine the overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Additionally, we performed a prespecified multivariable Cox regression comparing survival outcomes between sccRCC and snccRCC.ResultsThe ORR for the entire cohort was 35.4% (95% confidence interval [CI]: 23.4%, 49.6%), including 8 (16.7%) patients (95% CI: 8.7%, 29.6%) who achieved a complete remission. The disease control rate was 52% (95% CI: 38.3%, 65.5%). In patients with sccRCC, the ORR was 39% (95% CI: 25.7%, 54.3%) and disease control rate 58.5% (43.4%, 72.2%). Among 7 snccRCC patients, only one (14.3%) achieved an objective partial response. At a median follow-up of 51.1 months, the median PFS was 4.9 months (95% CI: 2.7, 16.3) and the median OS was 28.4 months (95% CI: 15.8, NA) for the entire cohort. For patients with sccRCC, the median PFS was 8.9 months, with median OS of 30.1 months, compared with median PFS of 2.3 months (HR 0.25 [95% CI: 0.08, 0.78]; P= 0.0145) and median OS of 6.7 months (HR 0.13 [95% CI 0.04, 0.44]; P=0.0009) for patients with snccRCC.ConclusionICIs appear to be effective in sccRCC while the treatment of snccRCC remains challenging.     

Systemic inflammation response index (SIRI) as a predictive factor for overall survival in advanced soft tissue sarcoma treated with eribulin

BackgroundEribulin is a tubulin and microtubule-targeting drug that has clinical benefit in overall survival (OS) for patients with advanced soft tissue sarcoma. Eribulin's efficacy has been confirmed in several clinical trials, although no clinically useful biomarkers have been identified. We therefore sought to clarify the predictive factor of eribulin treatment, while focusing on systemic inflammation and immune response values.MethodsThis study included 33 advanced STS patients treated with eribulin between March 2016 and September 2019. We evaluated the associations of clinical factors influencing the efficacy of eribulin treatment and systemic inflammatory and immune response, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the systemic inflammation response index (SIRI), and the prognostic nutrition index (PNI), with progression-free survival (PFS) and OS using the Kaplan–Meier method and log–rank test.ResultsNLR, LMR, PLR, SIRI, and PNI were unassociated with PFS. Compared with patients with SIRI <1.5, those with an SIRI ≥1.5 had a significantly shorter OS [median OS 15 months (95% confidence interval [CI] 8–not reached) vs. 7 months (95% CI 3–14), P = 0.04]. Moreover, the PFS tended to be shorter for patients with SIRI ≥1.5 who received chemotherapy after eribulin treatment than in those with SIRI >1.5 [median PFS 92.5 days (95% CI 27–204) vs. 133 days (95% CI 36–507), P = 0.08].ConclusionsHigh SIRI values may predict poorer overall survival and the efficacy of subsequent drugs after eribulin treatment among patients with advanced soft tissue sarcoma.     

UnCHAARTED territory: The role of docetaxel rechallenge following chemohormonal therapy for metastatic castration-sensitive prostate cancer

ObjectiveTo assess the effectiveness of docetaxel rechallenge (DR) for metastatic castration-resistant prostate cancer (mCRPC) following chemohormonal therapy for metastatic castrate-sensitive prostate cancer (mCSPC). Additionally, we sought to define clinical factors predicting treatment response.Patients and MethodsRetrospective analysis of men treated with docetaxel for mCSPC and then rechallenged in the mCRPC setting from four cancer centers in Ontario, Canada. Prostate specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) following DR were evaluated.ResultsFifty five patients were identified between 2015 and 2020. Prior to DR, 94.5% of patients received androgen-receptor axis targeted therapy, 20% received radium-223, and 1.8% received cabazitaxel. Among 54 evaluable patients, 27.8% had a PSA decline ≥50%. Median PFS was 4.1 months (95% CI, 2.1?4.8) and median OS from androgen deprivation therapy initiation was 38.3 months (95% CI, 32.9?41.0). A Gleason Score of ≥8 was an independent predictor of prolonged PFS (HR 0.32, 95% CI, 0.12?0.81; P=0.02).ConclusionsDR following chemohormonal therapy for mCSPC produced a meaningful PSA response in approximately one-quarter of patients, with relatively short PFS. The impact of Gleason Score on docetaxel response warrants further investigation.     

Anti-HER2 antibody prolongs overall survival disproportionally more than progression-free survival in HER2-Positive metastatic breast cancer patients

BackgroundThis meta-analysis aimed to test the hypothesis that the HER2-positive metastatic breast cancer (mBC) patients treated with anti-HER2 antibodies in trial intervention arms have a greater prolongation of overall survival (OS) than of progression-free survival (PFS) and this extra-prolongation of median survival time in OS relates specifically to the anti-HER2 antibody.MethodsThe NCBI/Pubmed and Cochrane databases were searched systematically for HER2-positive or mBC trials published in English during January 1999–November 2017. Treatment arms with shorter PFS were considered as the “control” arm, whereas those with longer PFS as the “test” arm. The between-treatment drug differences were grouped into nine categories. Groups with or without anti-HER2 antibodies were pooled respectively for comparisons. The interrelationships between PFS and OS hazard ratios (HRs) and median survival time differences were investigated by conducting fixed-effects and mixed-effects linear meta-regression analyses.ResultsTwenty-eight trials (10,928 patients) from 438 articles were collected, and four with missing data were excluded in meta-regression analysis. Overall median PFS (HR = 0.73, 95% CI: 0.68–0.78) and median OS (HR = 0.82, 95% CI: 0.77–0.87) weakly favored the longer PFS arm with a weak correlation between the PFS and OS HRs. However, the between-treatment drug difference was anti-HER2 antibody, the absolute increment in median OS time was double that of median PFS time (p < 0.001) and linearly correlated, which was not found with any non-anti-HER2 antibody drug differences.ConclusionsAnti-HER2 antibody in patients with HER2-positive mBC prolonged OS more than PFS and mandates further investigation.     

Impact of paclitaxel,cisplatin, and gemcitabine as first-line chemotherapy in cisplatin-fit and -unfit patients with advanced/metastatic urothelial carcinoma

PurposeThis study aimed to clarify the efficacy and toxicity of first-line combination treatment with paclitaxel, cisplatin, and gemcitabine (PCG) for advanced/metastatic urothelial carcinoma (UC) in cisplatin-unfit patients compared with cisplatin-fit patients.MethodsWe conducted a retrospective study of patients who received first-line PCG. Using international consensus criteria, patients were classified into cisplatin-fit and -unfit groups. Cisplatin-unfit patients received PCG with adjustment of the cisplatin dose after assessing 24-hour urinary creatinine clearance, without modifying the administration interval.ResultsFrom 2008 to 2017, 50 patients received first-line PCG, of whom 30 and 20 were classified into the cisplatin-fit and -unfit groups. After a median follow-up of 15.0 months, the median overall survival (OS) and progression-free survival (PFS) were 15.0 and 9.8 months in all patients, 15.0 and 10.0 months in the cisplatin-fit group, and 13.2 and 9.3 months in the cisplatin-unfit group, respectively. There was no significant difference in OS (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.69–2.54) or PFS (HR: 1.38, 95% CI: 0.74–2.55) between the groups. The overall response rate and complete response rate were 58% (95% CI: 43.2–71.8) and 32% (95% CI: 19.5–46.7) in all patients, and 55% (95% CI: 31.5–76.9) and 35% (95% CI: 15.4-59.2) in the cisplatin-unfit group, respectively. The common grade 3 of 4 adverse events experienced were neutropenia (78%), followed by thrombocytopenia (56%), anemia (46%), and febrile neutropenia (16%). The 24-hour urinary creatinine clearance did not differ significantly between the groups after one, two, or three courses of PCG.ConclusionsWe found no significant difference regarding OS and PFS between the cisplatin-fit patients with a full dose of cisplatin and -unfit patients with cisplatin-dose-adjusted chemotherapy. In select cisplatin-unfit patients, PCG with dose adjustment of cisplatin may be useful for treating advanced/metastatic UC without any significant adverse events or impaired renal function compared with cisplatin-fit patients with a full dose of cisplatin.     

The comparison of oncologic outcomes between metastatic upper tract urothelial carcinoma and urothelial carcinoma of the bladder after cisplatin-based chemotherapy

ObjectiveTo compare the oncologic outcomes and prognostic factors between metastatic upper tract urothelial carcinoma (UTUC) and UC of the bladder (UCB) after cisplatin-based chemotherapy.Materials and methodsWe retrospectively reviewed patients with metastatic UTUC and UCB after methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) or gemcitabine/cisplatin chemotherapy between 1997 and 2014 at Kaohsiung Chang Gung Memorial Hospital. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Univariate and multivariate analyses with Cox proportional hazard models were also performed to assess the effect of prognostic factors.ResultsTotally, 203 patients were enrolled into our study, including 120 patients with UTUC and 83 patients with UCB. For patients with UTUC, the median PFS was 7.3 months vs. 4.0 months (P<0.001), and the median OS was 17.0 months vs. 10.5 months (P<0.001) for MVAC and gemcitabine/cisplatin, respectively. For patients with UCB, the median PFS (P = 0.35) and OS (P = 0.06) of the 2 groups were insignificant. In multivariate analyses, number of metastatic sites was the identical prognostic factor for OS between UTUC (hazard ratio [HR] = 2.74; 95% CI: 1.63–4.62; P<0.001) and UCB (HR = 3.12; 95% CI: 1.52–6.39; P = 0.002). Presence of liver metastasis (HR = 1.84; 95% CI: 1.05–2.23; P = 0.03) and MVAC chemotherapy (HR = 0.54; 95% CI: 0.35–0.83; P<0.001) were significantly correlated to survival only for UTUC, not for UCB.ConclusionOur study suggests discordant oncologic outcomes and prognostic factors between metastatic UTUC and UCB after cisplatin-based chemotherapy. A prospective study is warranted to validate our results.     

Real-world treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in the United States

IntroductionThis large-scale, US-based study characterized real-world treatment patterns and clinical outcomes in patients with advanced or metastatic urothelial carcinoma (aUC).MethodsThis retrospective cohort analysis included patients with stage IV or node-positive aUC between January 1, 2011, and August 31, 2020, from an electronic health record-derived, de-identified database (Flatiron Health). Baseline characteristics and treatment patterns were assessed by first-line (1L) systemic treatment received and cisplatin eligibility status. Overall survival (OS) and progression-free survival (PFS) were evaluated.ResultsOf 8,183 patients included, 5,855 (71.6%) received systemic 1L therapy and 2,328 (28.4%) did not. Median (range) follow-up from aUC diagnosis was 9.7 (0.2-116.6) months. Of patients who received 1L systemic therapy, 30.1% were cisplatin-eligible, 39.2% were cisplatin-ineligible, 10.5% did not receive cisplatin despite qualifying ECOG PS and renal function, and cisplatin eligibility was unknown in 20.2%. Of those treated, 74.8% received 1L chemotherapy and 23.0% received 1L immuno-oncology–based monotherapy. Median OS (95% CI) was 14.5 (14.0-15.2) months in patients who received 1L systemic therapy and 6.8 (6.2-7.3) months in those who did not. Of those treated, cisplatin-ineligible patients had worse OS and PFS outcomes vs. other subgroups. Among cisplatin-ineligible patients, 1L immuno-oncology monotherapy (n = 865) was associated with worse OS and PFS outcomes than 1L chemotherapy (n = 1,369).ConclusionsMore than 25% of aUC patients did not receive 1L systemic therapy; of patients who were treated, most received chemotherapy, with less than 25% receiving immuno-oncology–based monotherapy. Overall, these results highlight the substantial unmet need in this population, specifically among cisplatin-ineligible patients.     

Baseline basophil and basophil-to-lymphocyte status is associated with clinical outcomes in metastatic hormone sensitive prostate cancer

BackgroundBiomarkers have the potential to provide clinical guidance, but there is limited data for biomarkers in metastatic hormone sensitive prostate cancer (mHSPC).MethodsWe performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014–2020) in the United States of America (USA). We collected demographics, disease characteristics, and laboratory data, including complete blood counts (CBC) at the start of upfront therapy. We evaluated overall survival (OS) and progression-free survival (PFS) associated with baseline lab values.Results165 patients were included with a median follow-up time of 33.5 months (mo). 105 (63.6%) had Gleason scores of 8-10 and 108 (65.9%) were classified as high-volume disease. 92 patients received upfront docetaxel (55.8%) and 73 received upfront abiraterone (44.2%). Univariate analyses (UVA) and multivariable analyses (MVA) identified worse clinical outcomes (CO) associated with elevated basophils and basophil-to-lymphocyte ratio (BLR). Based on MVA, elevated basophils (defined as ≥0.1, optimal cut) were associated with a hazard ratio (HR) of 3.51 (95% CI 1.65–7.43, P 0.001) for OS and HR of 1.88 (95% CI 1.05-3.38, P 0.034) for PFS. Our MVA also found that BLR ≥0.0142 was associated with HR 2.11 (95% CI 1.09–4.10, P 0.028) for OS; however, PFS was not statistically significant.ConclusionWe conclude that elevated baseline basophils and BLR are associated with worse clinical outcomes in mHSPC. Although results require further validation, BLR is a potential prognostic biomarker.     

Long term outcome data from the EORTC 75111-10114 ETF/BCG randomized phase II study: Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer,followed by T-DM1 after progression

IntroductionOlder patients are at higher risk of chemotherapy-induced toxicity, raising interest in less toxic anti-HER2 regimens for older persons with HER2-positive (HER2+) metastatic breast cancer (MBC).Patients and methodsThis phase II study randomized (1:1) patients with HER2+ MBC, aged 70+ or frail 60+, to first line chemotherapy with metronomic oral cyclophosphamide (M) + Trastuzumab (T) and Pertuzumab (P) or TP alone. T-DM1 was offered in case of progression.ResultsIn total, 39 and 41 patients were randomized to TP and TPM arm respectively. Median follow-up is 54.0 months. 24-month PFS was 18.7% (95% CI 8.2–32.4) and 28.7% (95% CI 15.8–43.0), respectively. A total of 49 (61.3%) patients died of whom 37 (75.5%) from disease progression; number of deaths per arm was 27 (69.2%) for TP and 22 (53.7%) for TPM. There was no significant difference in OS between the two arms (median OS TP vs TPM: 32.1 vs 37.5 months, p 0.25). Among the 40 patients who have started T-DM1 after disease progression on TP/TPM, PFS rate at 6 months after start of T-DM1 was 43.6% (95% CI: 27.7–58.5) and grade 3 or higher AE occurred in 18 pts (45%).ConclusionsMetronomic chemotherapy-based dual blockade (TPM), followed by T-DM1 after progression, provides an active and relatively well tolerated treatment option in an older/frail HER2+ MBC population, with a median survival of over 3 years. Nevertheless, the majority of this older/frail population died from breast cancer, highlighting the need for well tolerated and efficacious treatments in these patients.     

C-reactive protein and neutrophil-lymphocyte ratio are prognostic in metastatic clear-cell renal cell carcinoma patients treated with nivolumab

ObjectiveTo evaluate the impact of markers of systemic inflammation such as C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) on outcomes of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with nivolumab.Patients and methodsWe retrospectively evaluated m-ccRCC patients treated with nivolumab and collected known prognostic factors and survival data. We used Kaplan-Meier survival analysis and cox proportional hazards regression analysis to study prognostic factors for overall survival (OS) and progression-free survival (PFS) since start of nivolumab. Harrell's C-index was used to evaluate the models.ResultsWe included 113 patients. Median OS and PFS after initiation of nivolumab was 15 (interquartile range 7–28) and 4 months (interquartile range 3–11), respectively.Elevated baseline CRP was associated with worse OS (HR per 25 mg/l 1.35, 95% CI 1.16–1.52, P < 0.001) and PFS (HR per 25 mg/l 1.19, 95% CI 1.08–1.35, P = 0.001), independent from the international metastatic renal cell carcinoma database consortium (IMDC) prognostic criteria, increasing the model's C-index from 0.72 to 0.77 for OS and 0.59 to 0.62 for PFS.Elevated NLR was associated with worse OS (HR 1.10, 95% CI 1.04–1.17, P = 0.002) and PFS (HR 1.06, 95% CI 1.01–1.11, P = 0.03) independent from the other IMDC prognostic criteria. The model's C-index decreased from 0.72 to 0.70 for OS and increased from 0.59 to 0.60 for PFS.ConclusionsElevated baseline CRP and NLR predict worse OS and PFS on nivolumab in m-ccRCC patients. Including baseline CRP in the IMDC prognostic model improves its discriminatory power to predict OS and PFS since start of nivolumab.     

First-line vs second-line fulvestrant for hormone receptor-positive advanced breast cancer: A post-hoc analysis of the CONFIRM study

ObjectivesThe double-blind, phase III CONFIRM study (NCT00099437) evaluated fulvestrant 500 mg vs fulvestrant 250 mg in postmenopausal women with hormone receptor-positive locally advanced/metastatic breast cancer (LA/MBC). This post-hoc analysis investigated the efficacy and safety of fulvestrant given either first-line or second-line for advanced disease.Materials & methodsProgression-free survival (PFS) and overall survival (OS) with fulvestrant 500 mg vs fulvestrant 250 mg was evaluated using unadjusted log-rank tests in patients treated in the first- (progression during or within 12 months after completing adjuvant endocrine therapy; n = 387) and second-line (following endocrine therapy for LA/MBC; n = 343) settings.ResultsFirst-line fulvestrant 500 mg significantly prolonged PFS vs fulvestrant 250 mg (median PFS 5.6 vs 4.2 months; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.64–1.00; p = .047). Median PFS was numerically greater with second-line fulvestrant 500 mg vs fulvestrant 250 mg (7.9 vs 6.3 months; HR 0.80; 95% CI 0.64–1.02; p = .068). At data cut-off (75.5% maturity), median OS with first-line fulvestrant 500 mg was 23.2 vs 22.1 months with fulvestrant 250 mg (HR 0.87; 95% CI 0.70–1.10; p = .251), and 29.2 vs 22.8 months, respectively, in the second-line (HR 0.75; 95% CI 0.58–0.96; p = .020). The safety profile was broadly comparable between dose groups and across treatment lines, and consistent with the overall patient population.ConclusionThe superiority of fulvestrant 500 mg over fulvestrant 250 mg in patients with LA/MBC in CONFIRM was consistent in both the first- and second-line settings for PFS, and numerically greater in both settings for OS.     

Pazopanib in patients with metastatic renal cell carcinoma: a single-center,real-world,retrospective Chinese study

BackgroundThe efficacy and safety of pazopanib in patients diagnosed with metastatic renal cell carcinoma (mRCC) have been demonstrated by a Chinese subgroup analysis of the COMPARZ (Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma) trial. However, the real-world data are still unknown. This single-center, retrospective study was designed to verify the real-world effects of pazopanib in Chinese patients with mRCC.MethodsPatients with mRCC and a clinical decision to initiate pazopanib as first-line therapy were eligible. The primary endpoint was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and safety being evaluated as secondary endpoints. The effectiveness according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model, number of risk factors in the intermediate risk group, age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and the number and site of organ metastasis were also assessed.ResultsA total of 32 patients were enrolled, including 23 (71.9%) males and 9 (28.1%) females. The median age was 57 years (range 29–75 years). With a median follow-up time of 23.8 months, a median PFS of 18.3 months, and an ORR of 37.5%. Median OS was not reached, and the 1-, 2-, and 3-year overall survival rates were 90.6%, 78.1, and 65.6%, respectively. According to IMDC risk model, 37.5% were placed in the favorable risk (FR) subgroup, 56.2% (the majority) were placed in the intermediate risk (IR) subgroup, and 6.3% were placed in the poor risk (PR) subgroup. Compared with the IR and PR groups, the FR group achieved the best ORR (58.3%) and median PFS (22.1 months). Having 1 risk factor, ECOG PS <2, 1 organ metastasis site, and only lung metastasis associated with a higher ORR and better median PFS. The IMDC risk model and number of metastases were associated with PFS. The most common adverse events were change in hair color (69.0%), diarrhea (63%), and hypertension (50%).ConclusionsPazopanib showed efficacy and safety in real-world Chinese mRCC patients.     

Trastuzumab,Pertuzumab, and Docetaxel as the First Line for HER-2-Positive Metastatic Breast Cancer among Arabs

IntroductionHuman epidermal growth factor receptor 2 (HER-2) targeted therapy regimens can improve tumor response in HER-2-positive metastatic breast cancer (MBC), with overall survival benefits.ObjectiveWe evaluated the efficacy of dual HER-2 blockade combined with chemotherapy for HER-2-positive MBC patients as a first-line therapy in our patient population.Patients and MethodsWe identified 75 patients at King Faisal Specialist Hospital and Research Center that received trastuzumab, pertuzumab, and docetaxel as a first-line therapy in HER-2 positive MBC in 2013–2016.ResultsMedian age at diagnosis was 45 years; 54.7% were estrogen receptor (ER)-positive. 10% of patients presented with only bone metastasis. The median follow-up time was 36 months with an objective response rate of 74.7% (complete response [CR] 18.7%; partial response [PR] 56%). The 5-year progression-free survival (PFS) and overall survival (OS) were 21% and 71.9% respectively, with a median PFS of 36 months (95% confidence interval [CI] 23.6–48.4). The 5-year OS for ER-negative and ER-positive patients was 93.9% and 59.4% respectively (p = 0.189); 23 patients experienced grade 1/2 toxicity and 2 patients had grade 3/4 toxicity. In terms of OS and PFS, the site of metastasis did not make any significant difference.ConclusionsFirst line pertuzumab, trastuzumab, and docetaxel for HER-2-positive MBC patients was found to be an effective and safe therapy in the Saudi population. This finding was consistent with the results seen in the CLEOPATRA trials.     

First-line bevacizumab-containing therapy for HER2-negative locally advanced/metastatic breast cancer: Real-world experience from >2000 patients treated in the multicentre AVANTI study

AimThe multicentre non-interventional AVANTI study assessed safety, effectiveness and patient-reported outcomes with approved first-line bevacizumab-containing regimens for HER2-negative locally recurrent/metastatic breast cancer (LR/MBC) in German routine oncology practice.MethodsEligible patients had HER2-negative LR/MBC, no bevacizumab contraindications and no prior chemotherapy for LR/MBC. Chemotherapy schedule, diagnostics and follow-up were at physicians’ discretion. Data were collected for 1 year after starting bevacizumab, then every 6 months for 1.5 years (maximum follow-up: 2.5 years). Patients and physicians rated treatment satisfaction. Subgroup analyses were prespecified in clinically relevant populations, including triple-negative breast cancer (TNBC).ResultsBetween November 1, 2009 and April 30, 2016, 2065 eligible patients at 346 centres received bevacizumab with paclitaxel or capecitabine. Patients receiving bevacizumab–capecitabine were less likely to have de novo disease and more likely to have TNBC, age ≥60 years and prior anthracycline/taxane and/or endocrine therapy. Median PFS was 12.6 (95% CI 11.9–13.2) months (12.8 with bevacizumab–paclitaxel, 10.5 with bevacizumab–capecitabine); median OS was 23.9 (95% CI 22.2–25.1) months. Outcomes were worse in patients with TNBC, prior anthracycline/taxane or prior endocrine therapy. Grade ≥3 adverse events occurred in 27% of patients. Treatment was discontinued for adverse events in 15%. Treatment satisfaction was rated as good or better by 304/394 responding patients (77%) at week 54 and in 1393/2065 patients (67%) by physicians overall.ConclusionsIn routine clinical practice, effectiveness and safety of first-line bevacizumab-containing therapy for LR/MBC were consistent with experience from phase III trials. Patient and physician treatment satisfaction showed high concordance.     

T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer

BackgroundWe reported the results of an Italian large retrospective analysis that evaluated the effectiveness and safety of T-DM1 in ‘field-practice’ breast cancer patients. We performed a sub-analysis to investigate the clinical activity of T-DM1 in patients with brain metastases (BMs).MethodsThe records of 87 adult women with HER2-positive breast cancer and BMs treated with T-DM1 were reviewed. Their clinical outcomes were compared with those of 216 patients without central nervous system (CNS) involvement.ResultsResponse to T-DM1 treatment in BMs was available for 53 patients in the BM group (60.9%): two patients reported a complete response (3.8%), 11 patients obtained partial response (20.7%; overall response rate: 24.5%), 16 patients had a stable disease (30.1%). Regarding extracranial disease, a total of 77 and 191 patients were evaluable for response in BM group and non-BM group, respectively. The overall response rate was 35.1% in the BM group and 38.3% in the non-BM group; disease control rate was 53.3% and 66.6%, respectively.At a median follow-up of 16 months (range: 1–55), median cumulative progression-free survival (PFS) was 7 months (95% CI: 5.4–8.6) in the BM group and 8 months (95% CI: 5.7–10.3) in the non-BM group. In the second-line setting, PFS was 5 (95% CI: 3.1–6.9) versus 11 (95% CI: 7.1–14.9) months (p = 0.01). Overall survival was 14 months (95% CI: 12.2–15.8) in the BM group and 32 months (95% CI: 24.4–39.6) in the non-BM group (p < 0.0001).ConclusionsT-DM1 is active in breast cancer patients with BMs.     

Serum testosterone levels and testosterone ‘bounce’ phenomenon predict response to novel anti-androgen therapies in castration-resistant prostate cancer

BackgroundThe relevance of continuous testosterone (TT) monitoring in castration-resistant prostate cancer (CRPC) remains in question.ObjectiveTo determine if TT levels before and during novel anti-androgen therapies (NAAT), and the TT 'bounce' phenomenon may predict treatment response in CRPC.Materials and methodsFrom 2014 through 2018, we identified 92 CRPC patients treated with either Abiraterone or Enzalutamide from a prospectively maintained cancer registry. The TT levels measured before and during NAAT were correlated with the oncological outcomes, determined by PSA response (% change), PSA progression-free survival (PFS) and overall survival (OS).Results and limitationsAt CRPC, 58 (63.0%) and 34 (37.0%) patients opted for Abiraterone and Enzalutamide respectively. Median TT levels at CRPC status before and during NAAT were 10.37 ng/dl and 20.46 ng/dl respectively. PSA response was superior in patients with a higher TT before NAAT (P:0.048, median difference: 18.22%, 95% CI 0.70 – 40.37) and longer time to CRPC (P: 0.041, median difference: 15.31%, 95% CI 1.84 –34.84), with a trend towards lower TT during NAAT (P: 0.062). Over a follow up of 33.0 months, 65 patients (70.7%) developed PSA progression. PSA PFS was longer in patients with higher TT before NAAT (16.3 vs. 10.8 months; P: 0.023), lower TT during NAAT (17.0 vs. 9.1 months; P: 0.001), and longer time to CRPC (13.4 vs. 8.0 months; P: 0.032). Importantly, better OS was observed in lower TT during NAAT (45.0 vs. 33.0 months; P:0.029) and longer time to CRPC (43.0 vs. 31.0 months; P: 0.025). The TT ‘bounce’ phenomenon was observed in 28 patients (33.3%), and was associated with a poorer PSA response (P: 0.029, median difference: 18.90%, 95% CI 3.83 – 41.45), shorter PSA PFS (8.6 vs 15.2 months, P: 0.002) and shorter OS (29.0 vs. 45.0 months, P: 0.012).ConclusionIn CRPC patients, TT behaviors before and during NAAT, and the ‘bounce’ phenomenon continue to predict treatment response and could guide clinical decisions.     

Phase II study of intravenous vinflunine after failure of first-line vinorelbine based regimen for advanced breast cancer

PurposeThis open label phase II study evaluated the safety and efficacy of vinflunine in patients with breast cancer previously treated with a vinorelbine-based regimen and who progressed during or within 6 months of completing this chemotherapy.Patients and methodsThirty eight patients received vinflunine 320 mg/m² once every 3 weeks. The primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety.ResultsORR was 8.3% (95% CI: 1.75–22.4) and DCR was 75% (95% CI: 57.8–87.9). PFS was 4.0 months (95% CI: 2.5–6.1) and OS was 13.6 months (95% CI: 8.7–18.9).Toxicities not hampering dose intensity were as expected neutropenia (75.6% of patients), fatigue (44.7%), constipation (28.9%) and abdominal pain (26.3%).ConclusionVinflunine demonstrated antitumour activity and can be safely administered in breast cancer patients refractory/resistant to vinorelbine.     

A randomized phase II trial of trastuzumab plus capecitabine versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxanes: WJOG6110B/ELTOP

BackgroundFor human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies.Patients and methodsWomen with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX). The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and the objective response rate (ORR). To explore the predictive value of the differential benefit of anti-HER2 drugs, PIK3CA mutations were assessed using circulating tumor DNA.ResultsEighty-six patients (43 in each arm) were enrolled. The median PFS was 6.1 months in the HX arm and 7.1 months in the LX arm (hazard ratio, 0.81; 90% CI, 0.55–1.21; p = 0.39); the median OS was 31.0 months in the HX arm and was not reached in the LX arm (hazard ratio, 0.58; 95% CI, 0.26–1.31; p = 0.18). The ORR was 40% in the HX arm and 41% in the LX arm. PIK3CA mutations were detected in 23% of the 35 analyzed patients, and in patients without PIK3CA mutations, LX yielded relatively longer PFS and OS than HX.ConclusionIn women with HER2-positive MBC previously treated with trastuzumab and taxanes, no significant differences in PFS and OS were observed between patients treated with LX and HX.Trial registration numberUMIN000005219.