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A randomized trial involving patients with metastatic prostate cancer whose disease progressed after receipt of docetaxel and hormonal therapy showed that cabazitaxel was superior to an androgen-signaling–targeted agent in extending imaging-based progression-free survival, overall survival, and PSA response.

Background Metastatic castration‐resistant prostate cancer (mCRPC) patients have a poor prognosis, and curcumin is known to have antineoplastic properties. On the basis of previous phase I and phase II studies, we investigated whether the association of curcumin with docetaxel could improve prognosis among mCRPC patients. Methods A total of 50 mCRPC patients (included from June 2014 to July 2016) treated with docetaxel in association with oral curcumin (6 g/d for 7 days every 3 weeks) versus placebo were included in this double‐blind, randomized, phase II study. The primary endpoint was to evaluate the time to progression. Among the secondary endpoints, compliance, overall survival, prostate‐specific antigen (PSA) response, safety, curcumin absorption, and quality of life were investigated. An interim analysis was planned in the modified intention‐to‐treat population with data at 6 months (22 patients per arm). Results Despite good compliance and a verified absorption of curcumin, no difference was shown for our primary endpoint: progression‐free survival (PFS) between the placebo and curcumin groups was, respectively, 5.3 months versus 3.7 months, p = 0.75. Similarly, no difference was observed for the secondary objectives: PSA response rate (p = 0.88), overall survival (p = 0.50), and quality of life (p = 0.49 and p = 0.47). Conclusion Even though our previous studies and data in the literature seemed to support an association between curcumin and cancer therapies in order to improve patient outcome and prognosis, the results from this interim analysis clearly showed that adding curcumin to mCRPC patients’ treatment strategies was not efficacious. The study was discontinued on the grounds of futility. In this manuscript, we present the result of the interim analysis of our study conducted in metastatic castration‐resistant prostate cancer (mCRPC) patients. According to previous studies, we investigated whether the association of curcumin to docetaxel could improve prognosis among patients. This study is the first one to explore the efficacy of curcumin in mCRPC treated with docetaxel, with the assessment of serum curcumin levels. The results from this phase II study with such a posology lead us to conclude that curcumin in association with docetaxel does not improve mCRPC patients, nor does it improve progression‐free survival or overall survival.

Purpose A major question when treating HR+/HER2− metastatic breast cancer (MBC) is whether early introduction of chemotherapy (CT) increases endocrine resistance. We aimed to describe progression-free survival (PFS) under first endocrine therapy (ET) depending on whether given before or after CT in a large nationwide cohort, in the pre-CDK era. Methods The real-life retrospective ESME database includes all patients with MBC whose first-line treatment was initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. Our primary objective was to compare PFS from start of first ET in patients with HR+/HER2− MBC who received ET or CT first. Results We identified 6293 patients who received at least one ET line during their first two therapeutic lines for MBC. As first-line therapy, 3832 (60.9%) received ET alone (ET1 1st group), whilst 2461 (39.1%) received CT, including 2024 patients (32.2%) with maintenance ET after CT (ET1 after CT group). Median PFS under first ET was 12.4 months (95% CI 11.9–13.1) in ET 1st group vs. 12.6 months in ET1 after CT group (95% CI 12.1–13.4), HR 0.96 (95% CI 0.90–1.01, P  = 0.1277). Conclusions PFS under first ET appears identical whether prescribed before or after chemotherapy. These data suggest chemotherapy does not promote endocrine resistance.

Background: Bone-only (BO) metastatic breast cancer (MBC) is considered a more favorable entity than other MBC presentations. However, only few retrospective series and data from selected randomized controlled trials have been reported so far. Methods: Using the French national multicenter ESME (Epidemiological Strategy and Medico Economics) Data Platform, the primary objective of our study was to compare the overall survival (OS) of patients with BO versus non-BO MBC at diagnosis, with adjustment on main prognostic factors using a propensity score. Secondary objectives were to compare first-line progression-free survival (PFS1), describe treatment patterns, and estimate factors associated with OS. Results: Out of 20,095 eligible women, 5041 (22.4%) patients had BO disease [hormone-receptor positive (HR+)/human epidermal growth-factor-receptor-2 negative (HER2−), n = 4 102/13,229 (31%); HER2+, n = 644/3909 (16.5%); HR−/HER2−, n = 295/2 957 (10%)]. BO MBC patients had a better adjusted OS compared with non-BO MBC [52.1 months (95% confidence interval (CI) 50.3–54.1) versus 34.7 months (95% CI 34.0–35.6) respectively]. The 5-year OS rate of BO MBC patients was 43.4% (95% CI 41.7–45.2). They also had a better PFS1 [13.1 months (95% CI 12.6–13.8) versus 8.5 months (95% CI 8.3–8.7), respectively]. This observation could be repeated in all subtypes. BO disease was an independent prognostic factor of OS [hazard ratio 0.68 (95% CI 0.65–0.72), p < 0.0001]. Results were concordant in all analyses. Conclusion: BO MBC patients have better outcomes compared with non-BO MBC, consistently, through all MBC subtypes.

Background: As a result of progress in diagnosis and treatment, there is a growing prevalence of metastatic breast cancer (MBC) with isolated CNS metastases. This study describes the largest-to-date real-life cohort of this clinical setting and compares it to other clinical presentations. Methods: We retrospectively analysed the French Epidemiological Strategy and Medical Economics (ESME) MBC database including patients who initiated treatment for MBC between 2008 and 2016. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Descriptive statistics and multivariate Cox model were used. Results: Of 22,266 patients, 647 (2.9%) and 929 (4.2%) patients had isolated first-site CNS metastases or combined with extra-CNS metastases, with longer OS for the group with isolated CNS metastases (16.9 versus 13.9 months, adjusted HR = 1.69 (95% CI: 1.50–1.91), p < 0.001). Among the 541 (2.4%) patients with isolated CNS metastases and no intrathecal therapy (excluding leptomeningeal metastases), HER2+ cases were preponderant over TN or HR+ /HER2− cases (41.6% versus 26.1% versus 28.5%, respectively, p < 0.01). The treatment strategy consisted of a combination of local treatment and systemic therapy (49.2%), local treatment only (35.5%) or systemic therapy only (11.4%), or symptomatic therapy only (3.9%). Median PFS was 6.1 months (95% CI: 5.7–6.8). Median OS was 20.7 months (95% CI: 17.3–24.3), reaching 37.9 months (95% CI: 25.9–47.6) in the HR+ /HER2+ subgroup. Older age, TN subtype, MBC-free interval of 6–12 months, lower performance status, and WBRT were associated with poorer survival. Patients who received systemic therapy within 3 months from MBC diagnosis had longer OS (24.1 versus 16.1 months, p = 0.031), but this was not significant on multivariate analysis [HR = 1.0 (95% CI: 0.7–1.3), p = 0.806]. Conclusions: Patients with isolated CNS metastases at MBC diagnosis represent a distinct population for which the role of systemic therapy needs to be further investigated in prospective studies.

Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane. In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0–2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436. Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6–13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7–46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment. Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations. Janssen Research & Development.

Background The ZOHé study was a prospective, non-interventional, multicentre study in France to assess the use of biosimilar filgrastim Zarzio® (Sandoz filgrastim) in routine clinical practice in patients at risk of neutropenia-inducing chemotherapy (CT). Methods Patients ≥ 18 years undergoing CT for a malignant disease and with a first prescription for Zarzio® were enrolled in two cohorts according to tumour type: solid tumour or haematological malignancy; results from the solid tumour cohort are reported here. Analyses primarily described the prescription and use of Zarzio® in current practice, and also included identification of factors linked to prescription for primary prophylaxis and comparison of Zarzio® use in relation to European Organisation for Research and Treatment of Cancer (EORTC) guidelines. Results Responses were obtained from 125 physicians and 1179 patients with solid tumours, allowing robust statistical analysis of the data. Use of Zarzio® in clinical practice was relatively standardised and followed label indication. The patient profile was in line with EORTC guidelines for granulocyte colony-stimulating factor (G-CSF) febrile neutropenia (FN) prophylaxis, and the majority of patients had ≥ 1 EORTC factor(s) for increased risk of febrile neutropenia. Some patients (10.8%) received Zarzio® despite receiving CT regimens categorised in guidelines as low (< 10%) FN risk (‘over prophylaxis’). Nearly half of patients’ CT regimens did not have a recommended FN risk category. Zarzio® was commonly initiated as primary prophylaxis; initiation in Cycle ≥ 2 of the current line of CT was associated more with a history of neutropenia. The safety profile of Zarzio® was confirmed. Conclusions Use of Zarzio® in routine clinical practice is generally in line with EORTC guidelines for prophylaxis of CT-induced neutropenia. Patient-related risk factors appear to be a stronger driver of clinicians’ decision to initiate Zarzio® than CT risk category for FN. The intrinsic risk of FN associated with a specific CT protocol is often miscategorised by physicians. In contrast to earlier reports of underuse of G-CSF prophylaxis, over prophylaxis is observed in a small subgroup of patients with FN risk of < 10%.

Estramustine phosphate is a mustard-oestradiol conjugate, and has hormonal and non-hormonal effects. In phase II trials of patients with cancer, response to microtubule inhibitors increases when these drugs are combined with estramustine. We aimed to assess whether combining estramustine with chemotherapy increases survival in patients with castration-refractory prostate cancer. We systematically searched for randomised clinical trials that compared chemotherapy regimens with and without estramustine in patients with histologically-proven prostate cancer and were published between 1966 and 2004. Data from these studies were verified centrally and updated individual patient data were analysed. The primary endpoint was overall survival. Secondary endpoints were prostate-specific antigen (PSA) response, time to PSA progression, and toxicity. A Cox regression model that was stratified by trial and adjusted for covariates at baseline was used. The initial search identified seven eligible trials that included 742 patients, from which data from five trials including 605 patients had been collected. Individual patient data from two trials (137 patients) were no longer available. The 605 patients had been accrued between Jan 1, 1993 and Dec 1, 2003 and randomly assigned to chemotherapy plus estramustine or to chemotherapy without estramustine. Chemotherapy (with or without estramustine) consisted of docetaxel, paclitaxel, ixabepilone, and vinblastine. Median follow-up was 2·8 years (range 0·0–3·4), and 510 deaths had occurred by the end of follow-up. Cox regression analysis stratified by trial showed that concentrations of serum haemoglobin (p<0·0001), use of chemotherapy plus estramustine (p=0·008), performance status (p=0·002), and serum PSA concentrations (p=0·04) were associated independently with overall survival. Overall survival was significantly better in patients assigned chemotherapy plus estramustine (adjusted hazard ratio [HR] 0·77 [95% CI 0·63–0·93], p=0·008). Estimated absolute increase in overall survival when estramustine was added to chemotherapy was 9·5% (SE 4·0) at 1 year after randomisation. We did not note a significant association between treatment effect on overall survival and age, concentration of serum haemoglobin, performance status, or serum PSA concentration. Patients who received chemotherapy plus estramustine had a better PSA response than those who received chemotherapy without estramustine (RR 0·53 [0·38–0·72], p<0·0001). Time to PSA progression was significantly longer in patients assigned chemotherapy plus estramustine than in those assigned chemotherapy without estramustine (HR 0·74 [0·58–0·94], p=0·01). Patients assigned chemotherapy and estramustine had more grade 3 or grade 4 thromboembolic events compared with those assigned chemotherapy without estramustine (12 of 271 vs 1 of 275). In patients with castration-refractory prostate cancer, addition of estramustine to chemotherapy increases time to PSA progression and overall survival compared with chemotherapy without estramustine. However, this benefit should be balanced with the risk of increased thromboembolic events in patients who receive estramustine and chemotherapy in combination compared with chemotherapy without estramustine.

Poor prognosis germ-cell tumours are only cured in about half of patients. We aimed to assess whether treatment intensification based on an early tumour marker decline will improve progression-free survival for patients with germ-cell tumours. In this phase 3, multicentre, randomised trial, patients were enrolled from France (20 centres), USA (one centre), and Slovakia (one centre). Patients were eligible if they were older than 16 years, had evidence of testicular, retroperitoneal, or mediastinal non-seminomatous germ cell tumours based on histological findings or clinical evidence and highly elevated serum human chorionic gonadotropin or alfa-fetoprotein concentrations that matched International Germ Cell Cancer Consensus Group poor prognosis criteria. After one cycle of BEP (intravenous cisplatin [20 mg/m2 per day for 5 days], etoposide [100 mg/m2 per day for 5 days], and intramuscular or intravenous bleomycin [30 mg per day on days 1, 8, and 15]), patients' human chorionic gonadotropin and alfa-fetoprotein concentrations were measured at day 18–21. Patients with a favourable decline in human chorionic gonadotropin and alfa-fetoprotein continued BEP (Fav-BEP group) for 3 additonal cycles, whereas patients with an unfavourable decline were randomly assigned (1:1) to receive either BEP (Unfav-BEP group) or a dose-dense regimen (Unfav-dose-dense group), consisting of intravenous paclitaxel (175 mg/m2 over 3 h on day 1) before BEP plus intravenous oxaliplatin (130 mg/m2 over 3 h on day 10; two cycles), followed by intravenous cisplatin (100 mg/m2 over 2 h on day 1), intravenous ifosfamide (2 g/m2 over 3 h on days 10, 12, and 14), plus mesna (500 mg/m2 at 0, 3, 7 and 11 h), and bleomycin (25 units per day, by continuous infusion for 5 days on days 10–14; two cycles), with granulocyte-colony stimulating factor (lenograstim) support. Centrally blocked computer-generated randomisation stratified by centre was used. The primary endpoint was progression-free survival and the efficacy analysis was done in the intention-to-treat population. The planned trial accrual was completed in May, 2012, and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00104676. Between Nov 28, 2003, and May 16, 2012, 263 patients were enrolled and 254 were available for tumour marker assessment. Of these 51 (20%) had a favourable marker assessment, and 203 (80%) had an unfavourable tumour marker decline; 105 were randomly assigned to the Unfav-dose-dense group and 98 to the Unfav-BEP group. 3-year progression-free survival was 59% (95% CI 49–68) in the Unfav-dose-dense group versus 48% (38–59) in the Unfav-BEP group (HR 0·66, 95% CI 0·44–1·00, p=0·05). 3-year progression-free survival was 70% (95% CI 57–81) in the Fav-BEP group (HR 0·66, 95% CI 0·49–0·88, p=0·01 for progression-free survival compared with the Unfav-BEP group). More grade 3–4 neurotoxic events (seven [7%] vs one [1%]) and haematotoxic events occurred in the Unfav-dose-dense group compared with in the Unfav-BEP group; there was no difference in grade 1–2 febrile neutropenia (18 [17%] vs 18 [18%]) or toxic deaths (one [1%] in both groups). Salvage high-dose chemotherapy plus a stem-cell transplant was required in six (6%) patients in the Unfav-dose-dense group and 16 (16%) in the Unfav-BEP group. Personalised treatment with chemotherapy intensification reduces the risk of progression or death in patients with poor prognosis germ-cell tumours and an unfavourable tumour marker decline. Institut National du Cancer (Programme Hospitalier de Recherche Clinique).

Introduction Improvement in overall survival (OS) by locoregional treatment (LRT) of the primary tumor in de novo metastatic breast cancer (MBC) patients remains controversial. Objective The aim of our study was to evaluate the impact of LRT on OS in a large retrospective cohort of de novo MBC patients, with regard to immunohistochemical characteristics and pattern of metastatic dissemination. Methods We conducted a multicentric retrospective study of patients diagnosed with de novo MBC selected from the French Epidemiological Strategy and Medical Economics MBC database (NCT03275311) between 2008 and 2014. Overall, 4276 women were included in the study. LRT comprised either radiotherapy, surgery, or both. Results LRT was used in 40% of patients. Compared with no LRT, patients who received LRT were younger ( p  < 0.0001) and were more likely to have only one metastatic site ( p  < 0.0001) or bone-only metastases ( p  < 0.0001). LRT was associated with a significantly better OS based on landmark multivariate analysis at 1-year (hazard ratio 0.65, 95% confidence interval 0.55–0.76, p  < 0.001). Similar results were observed in all sensitivity analyses, including propensity score matching. In subgroup analysis, LRT was associated with better OS in patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (61.6 vs. 45.9 months, p  < 0.001) and HER2-positive tumors (77.2 vs. 52.6 months, p  = 0.008), but not in triple-negative tumors (19 vs. 18.6 months, p  = 0.54), and was also associated with a reduction in the risk of death in visceral metastatic patients ( p  < 0.001). Conclusions LRT was associated with a significantly better OS in de novo MBC patients, including patients with visceral involvement at diagnosis; however, LRT did not impact OS in triple-negative MBC.