Alpelisib for PIK3CA-mutated advanced gynecological cancers: First clues of clinical activity.

OBJECTIVE: Recurrent gynecological tumors (e.g., endometrial, and ovarian cancers) are incurable diseases; therefore, new treatment options are urgently needed. The PTEN-AKT-PI3K pathway is frequently altered in these tumors, representing a potential treatment target. Alpelisib is an α-specific PI3K inhibitor approved in PIK3CA-mutated advanced breast cancer. We report outcomes from a large series of patients with PIK3CA-mutated gynecological cancers prospectively treated with alpelisib within a controlled program. METHODS: From April 2021 to December 2022, 36 patients with PIK3CA-mutated advanced gynecological cancers received alpelisib 300 mg orally once daily. Objective response (ORR) and disease control (DCR) rates provided measure of the antitumor activity of alpelisib, the primary objective of the study. RESULTS: Included patients had endometrial (17/36 [47%]), ovarian (10/36 [28%]), or other gynecological cancers (9/36 [25%]). Most patients had received 2-3 prior systemic treatments (endometrial, 47·2%; ovarian, 60%; other, 56%), and presented with visceral metastases at baseline (82%, 70%, and 56%, respectively). Overall, 17 different PIK3CA mutations were found, including 53% in the kinase domain (most commonly H1047R) and 36% in the helical domain (most commonly E545K). Overall, the ORR was 28% and DCR was 61%, with the greatest benefit observed in patients with endometrial cancer (35% and 71%, respectively). CONCLUSION: Alpelisib represents an active treatment option in patients with recurrent gynecological cancers harboring a PIK3CA mutation. These findings support the need of biomarker-driven randomized trials of PI3K inhibitors in gynecological cancers.

Reirradiation with radiosurgery or stereotactic fractionated radiotherapy in association with regorafenib in recurrent glioblastoma.

PURPOSE: No standard treatment has yet been established for recurrent glioblastoma (GBM). In this context, the aim of the current study was to evaluate safety and efficacy of reirradiation (re-RT) by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association with regorafenib. METHODS: Patients with a histological or radiological diagnosis of recurrent GBM who received re-RT by SRS/FSRT and regorafenib as second-line systemic therapy were included in the analysis. RESULTS: From January 2020 to December 2022, 21 patients were evaluated. The median time between primary/adjuvant RT and disease recurrence was 8 months (range 5-20). Median re-RT dose was 24 Gy (range 18-36 Gy) for a median number of 5 fractions (range 1-6). Median regorafenib treatment duration was 12 weeks (range 3-26). Re-RT was administered before starting regorafenib or in the week off regorafenib during the course of chemotherapy. The median and the 6­month overall survival (OS) from recurrence were 8.4 months (95% confidence interval [CI] 6.9-12.7 months) and 75% (95% CI 50.9-89.1%), respectively. The median progression-free survival (PFS) from recurrence was 6 months (95% CI 3.7-8.5 months). The most frequent side effects were asthenia that occurred in 10 patients (8 cases of grade 2 and 2 cases of grade 3), and hand-foot skin reaction (2 patients grade 3, 3 patients grade 2). Adverse events led to permanent regorafenib discontinuation in 2 cases, while in 5/21 cases (23.8%), a dose reduction was administered. One patient experienced dehiscence of the surgical wound after reintervention and during regorafenib treatment, while another patient reported intestinal perforation that required hospitalization. CONCLUSION: For recurrent GBM, re-RT with SRT/FSRT plus regorafenib is a safe treatment. Prospective trials are necessary.

Impact of influenza vaccination on survival of patients with advanced cancer receiving immune checkpoint inhibitors (INVIDIa-2): final results of the multicentre, prospective, observational study.

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration. Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR). Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5-34.6) in vaccinated vs. 20.9 months (16.6-25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4-14.6) vs. 9.6 months (CI 7.9-11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62-0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11-1.96; p = 0.007). Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity. Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus.

Radiosurgery and Stereotactic Brain Radiotherapy with Systemic Therapy in Recurrent High-Grade Gliomas: Is It Feasible? Therapeutic Strategies in Recurrent High-Grade Gliomas.

PURPOSE: For recurrent high-grade gliomas (HGG), no standard therapeutic approach has been reported; thus, surgery, chemotherapy, and re-irradiation (re-RT) may all be proposed. The aim of the study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association to chemotherapy in patients with recurrent HGG. MATERIAL/METHODS: All patients with histological diagnosis of HGG that suffered by recurrent disease diagnosed by magnetic resonance imaging (MRI), according to Response Assessment in Neuro-Oncology (RANO) criteria, after primary/adjuvant chemo-radiotherapy treatment and underwent to re-RT by SRS/FSRT were included in the analysis. Second-line chemotherapy was administered. Outcomes were evaluated by neurological examination and brain MRI performed 1 month after re-RT and then every 2-3 months. RESULTS: From November 2019 to September 2021, 30 patients presenting recurrent HGG underwent re-RT. Median dose was 24 Gy (range 15-36 Gy), and median fractions was 5 (range 1-6). Twenty-one patients (70%) had RPA class ≤ IV. One patient had a histological diagnosis of anaplastic oligodendroglioma, 24 patients (80%) were affected by glioblastoma (GBM) including 3 cases of multifocal form, and 5 patients (17%) by anaplastic astrocytoma. Median time between primary/adjuvant RT and disease recurrence was 8 months. In six cases (20%) re-operation was performed, and in most cases (87%), a second line of systemic therapy was administrated. At a median follow-up time from recurrence of 13 months (range 6-56 months), 10 patients (33%) were alive: 2 patients with partial response disease, 7 patients with stable disease, and 1 patient with out-field progression disease. Of the 20 patients who died (67%), 15 (75%) died for progression disease and 5 (25%) for other causes (3 due to septic event, 1 due to thrombo-embolic event, and 1 due to car accident). Median OS and PFS after recurrence were 12.1 and 11.2 months. Six-month and one-year OS were, respectively, 81% and 51%. No acute or late neurological side effects grade ≥ 2 and no case of radio-necrosis were reported. One patient experienced, after reintervention and during Regorafenib treatment (administered 40 days after surgery), dehiscence of the surgical wound. In three cases, grade 2 distal paresthesia was reported. Grade 3-4 hematologic toxicity occurred in seven cases. Three case of grade 5 toxicities during chemotherapy were reported: three septic events and one thrombo-embolic event. CONCLUSION: Re-RT with SRT/FSRT in association with second-line systemic therapy is a safe and feasible treatment for patients with HGG recurrence. Validation of these results by prospective studies is needed.

Non-surgical treatment of hilar cholangiocarcinoma.

Cancer of the biliary confluence also known as hilar cholangiocarcinoma (HC) or Klatskin tumor, is a rare type of neoplastic disease constituting approximately 40%-60% of intrahepatic malignancies, and 2% of all cancers. The prognosis is extremely poor and the majority of Klatskin tumors are deemed unresectable upon diagnosis. Most patients with unresectable bile duct cancer die within the first year after diagnosis, due to hepatic failure, and/or infectious complications secondary to biliary obstruction. Curative treatments include surgical resection and liver transplantation in highly selected patients. Nevertheless, very few patients are eligible for surgery or transplant at the time of diagnosis. For patients with unresectable HC, radiotherapy, chemotherapy, photodynamic therapy, and liver-directed minimally invasive procedures such as percutaneous image-guided ablation and intra-arterial chemoembolization are recommended treatment options. This review focuses on currently available treatment options for unresectable HC and discusses future perspectives that could optimize outcomes.

Current trends and perspectives in interventional radiology for gastrointestinal cancers.

Gastrointestinal (GI) cancers often require a multidisciplinary approach involving surgeons, endoscopists, oncologists, and interventional radiologists to diagnose and treat primitive cancers, metastases, and related complications. In this context, interventional radiology (IR) represents a useful minimally-invasive tool allowing to reach lesions that are not easily approachable with other techniques. In the last years, through the development of new devices, IR has become increasingly relevant in the context of a more comprehensive management of the oncologic patient. Arterial embolization, ablative techniques, and gene therapy represent useful and innovative IR tools in GI cancer treatment. Moreover, IR can be useful for the management of GI cancer-related complications, such as bleeding, abscesses, GI obstructions, and neurological pain. The aim of this study is to show the principal IR techniques for the diagnosis and treatment of GI cancers and related complications, as well as to describe the future perspectives of IR in this oncologic field.

Poor-Prognosis Patients Affected by Glioblastoma: Retrospective Study of Hypofractionated Radiotherapy with Simultaneous Integrated Boost and Concurrent/Adjuvant Temozolomide.

BACKGROUND: Glioblastoma (GBM) is a very poor-prognosis brain tumor. To date, maximal excision followed by radiochemotherapy, in 30 fractions, is the standard approach. Limited data are present in the literature about hypofractionated radiotherapy (hypo-RT) in GBM poor prognosis patients. Thus, this retrospective study was conducted to evaluate efficacy and toxicity of hypo-RT with simultaneous integrated boost (SIB) in association with temozolomide (TMZ) in this patient setting. METHODS: Poor-prognosis GBM patients underwent surgery (complete, subtotal or biopsy) followed by SIB-hypo-RT and concomitant/adjuvant TMZ. The prescription dose was 40.05 Gy (15 fractions) with a SIB of 52.5 Gy (3.5 Gy/fraction) on surgical cavity/residual/macroscopic disease. Volumetric modulated arc therapy was performed. RESULTS: From July 2019 to July 2021, 30 poor-prognosis patients affected by GBM were treated by SIB-hypo-RT; 25 were evaluated in the present analysis due to a minimum follow up of 6 months. The median age and KPS were 65 years and 60%, respectively. At the median follow-up time of 15 months (range 7-24), median and 1-year overall survival and progression-free survival were 13 months and 54%, and 8.4 months and 23%, respectively. No acute or late neurological side effects of grade ≥ 2 were reported. Grade 3-4 hematologic toxicity occurred in three cases. CONCLUSION: SIB-hypo-RT associated with TMZ in poor-prognosis patients affected by GBM is an effective and safe treatment. Prospective studies could be warranted.

Worldwide management of hepatocellular carcinoma during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has impacted hospital organization, with the necessity to quickly react to face the pandemic. The management of the oncological patient has been modified by necessity due to different allocation of nurses and doctors, requiring new strategies to guarantee the correct assistance to the patients. Hepatocellular carcinoma, considered as one of the most aggressive types of liver cancer, has also required a different management during this period in order to optimize the management of patients at risk for and with this cancer. The aim of this document is to review recommendations on hepatocellular carcinoma surveillance and management, including surgery, liver transplantation, interventional radiology, oncology, and radiotherapy. Publications and guidelines from the main scientific societies worldwide regarding the management of hepatocellular carcinoma during the COVID-19 pandemic were reviewed.

Radiofrequency ablation vs surgical resection in elderly patients with hepatocellular carcinoma in Milan criteria.

BACKGROUND: Surgical resection and radiofrequency ablation (RFA) represent two possible strategy in treatment of hepatocellular carcinoma (HCC) in Milan criteria. AIM: To evaluate short- and long-term outcome in elderly patients (> 70 years) with HCC in Milan criteria, which underwent liver resection (LR) or RFA. METHODS: The study included 594 patients with HCC in Milan criteria (429 in LR group and 165 in RFA group) managed in 10 European centers. Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching (PSM) and Cox regression. RESULTS: After PSM, we compared 136 patients in the LR group with 136 patients in the RFA group. Overall survival at 1, 3, and 5 years was 91%, 80%, and 76% in the LR group and 97%, 67%, and 41% in the RFA group respectively (P = 0.001). Disease-free survival at 1, 3, and 5 years was 84%, 60% and 44% for the LR group, and 63%, 36%, and 25% for the RFA group (P = 0.001).Postoperative Clavien-Dindo III-IV complications were lower in the RFA group (1% vs 11%, P = 0.001) in association with a shorter length of stay (2 d vs 7 d, P = 0.001).In multivariate analysis, Model for End-stage Liver Disease (MELD) score (> 10) [odds ratio (OR) = 1.89], increased value of international normalized ratio (> 1.3) (OR = 1.60), treatment with radiofrequency (OR = 1.46) ,and multiple nodules (OR = 1.19) were independent predictors of a poor overall survival while a high MELD score (> 10) (OR = 1.51) and radiofrequency (OR = 1.37) were independent factors associated with a higher recurrence rate. CONCLUSION: Despite a longer length of stay and a higher rate of severe postoperative complications, surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients (> 70 years) with HCC in Milan criteria.

INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: a multicenter prospective observational study (INVIDIa-2).

BACKGROUND: Until now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs). METHODS: The prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety. RESULTS: The study enrolled 1279 patients; 1188 patients were evaluable for the primary endpoint analysis. Of them, 48.9% (581) received influenza vaccination. The overall ILI incidence was 8.2% (98 patients). Vaccinated patients were significantly more frequently elderly (p<0.0001), males (p=0.004), with poor European Cooperative Oncology Group performance status (p=0.009), affected by lung cancer (p=0.01), and by other non-cancer comorbidities (p<0.0001) when compared with unvaccinated. ILI incidence was not different basing on influenza vaccination: the time-to-ILI was similar in vaccinated and unvaccinated patients (p=0.62). ILI complications were significantly less frequent for patients receiving the vaccination (11.8% vs 38.3% in unvaccinated, p=0.002). ILI-related intravenous therapies were significantly less frequent in vaccinated patients than in unvaccinated (11.8% vs 29.8%, p=0.027). ILI lethality was, respectively, 0% in vaccinated and 4.3% in unvaccinated patients. Vaccine-related adverse events were rare and mild (1.5%, grades 1-2). CONCLUSION: The INVIDIa-2 study results support a positive recommendation for influenza vaccination in patients with advanced cancer receiving immunotherapy.

The Role of Laparoscopic Surgery in Localized Pancreatic Neuroendocrine Tumours.

OPINION STATEMENT: Pancreatic neuroendocrine tumours (PNETs) are a rare and heterogeneous group of tumours with various clinical manifestations and biological behaviours. They represent approximately 2-4% of all pancreatic tumours, with an incidence of 2-3 cases per million people. PNETs are classified clinically as non-functional or functional, and pancreatic resection is recommended for lesions greater than 2 cm. The surgical approach can involve "typical" and "atypical" resections depending on the number, size and location of the tumour. Typical resections include pancreaticoduodenectomy, distal pancreatectomy enucleation and, rarely, total pancreatectomy. Atypical resections comprise central pancreatectomies or enucleations. Minimally invasive pancreatic resection has been proven to be technically feasible and safe in high-volume and specialized centres with highly skilled laparoscopic surgeons, with consolidated benefits for patients in the postoperative course. However, open and minimally invasive pancreatic surgery remains to have a high rate of complications; there is no specific technical contraindication to minimally invasive pancreatic surgery, but an appropriate patient selection is crucial to obtain satisfactory clinical and oncological outcomes.

Current status of non-surgical treatment of locally advanced pancreatic cancer.

Pancreatic cancer is the 7th leading cause of death due to cancer in industrialized countries and the 11th most common cancer globally, with 458918 new cases (2.5% of all cancers) and 432242 deaths (4.5% of all cancer deaths) in 2018. Unfortunately, 80% to 90% of the patients present with unresectable disease, and the reported 5-year survival rate range between 10% and 25%, even after successful resection with tumor-free margins. Systemic chemotherapy, radiotherapy, and minimally invasive image-guided procedures that have emerged over the past years, are used for the management of non-operable PC. This review focuses on currently available non-surgical options of locally advanced pancreatic cancer.

Metabolomics to Assess Response to Immune Checkpoint Inhibitors in Patients with Non-Small-Cell Lung Cancer.

In the treatment of advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitors have shown remarkable results. However, not all patients with NSCLC respond to this drug treatment or receive durable benefits. Thus, patient stratification and selection, as well as the identification of predictive biomarkers, represent pivotal aspects to address. In this framework, metabolomics can be used to support the discrimination between responders and non-responders. Here, metabolomics was used to analyze the sera samples from 50 patients with NSCL treated with immune checkpoint inhibitors. All the samples were collected before the beginning of the treatment and were analyzed by NMR spectroscopy and multivariate statistical analyses. Significantly, we show that the metabolomic fingerprint of serum acts as a predictive "collective" biomarker to immune checkpoint inhibitors response, being able to predict individual therapy outcome with > 80% accuracy. Metabolomics represents a potential strategy for the real-time selection and monitoring of patients treated with immunotherapy. The prospective identification of responders and non-responders could improve NSCLC treatment and patient stratification, thus avoiding ineffective therapeutic strategies.

Screening for Frailty in Older Patients With Early-Stage Solid Tumors: A Prospective Longitudinal Evaluation of Three Different Geriatric Tools.

BACKGROUND: Frailty increases the risk of adverse health outcomes and/or dying when exposed to a stressor, and routine frailty assessment is recommended to guide treatment decision. The Balducci frailty criteria (BFC) and Fried frailty criteria (FFC) are commonly used, but these are time consuming. Vulnerable Elders Survey-13 (VES-13) score of ≥7, a simple and resource conserving function-based scoring system, may be used instead. This prospective study evaluates the performance of VES-13 in parallel with BFC and FFC, to identify frailty in elderly patients with early-stage cancer. METHODS: Patients aged ≥70 years with early-stage solid tumors were classified as frail/nonfrail based on BFC (≥1 criteria), FFC (≥3 criteria), and VES-13 (score ≥ 7). All patients were assessed for functional decline and death. RESULTS: We evaluated 185 patients. FFC had a 17% frailty rate, whereas BFC and VES-13 both had 25%, with poor concordance seen between the three geriatric tools. FFC (hazard ratio = 1.99, p = .003) and VES-13 (hazard ratio = 2.81, p < .001) strongly discriminated for functional decline, whereas BFC (hazard ratio = 3.29, p < .001) had the highest discriminatory rate for deaths. BFC and VES-13 remained prognostic for overall survival in multivariate analysis correcting for age, tumor type, stage, and systemic treatment. CONCLUSIONS: A VES-13 score of ≥7 is a valuable discriminating tool for predicting functional decline or death and can be used as a frailty-screening tool among older cancer patients in centers with limited resources to conduct a comprehensive geriatric assessment.

An exceptional overall survival using bevacizumab beyond progression in a patient with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common malignancy and the leading cause of cancer death worldwide. In this report, we describe a patient with NSCLC who was treated with continuation of Bevacizumab (Bev) beyond progression to first-line Bev-based chemotherapy. The prolonged treatment with Bev by continuing the inhibition of VEGF beyond first-progression has a strong rationale. Nevertheless, few data exist regarding the efficacy and safety of Bev beyond first line of chemotherapy progression in NSCLC patients. Further studies including a large number of patients are needed, in order to select patients who could benefit from this approach.

Maintenance treatment with oral cyclophosphamide and bevacizumab in patients with recurrent epithelial ovarian cancer.

AIM: To evaluate the efficacy and safety of maintenance treatment with oral cyclophosphamide (Cy) and bevacizumab (Bev) in patients with recurrent ovarian cancer. PATIENTS & METHODS: Induction treatment consisted of cisplatin, epirubicin, Cy and Bev every 3 weeks, for a maximum of six cycles. Maintenance treatment consisted of oral Cy 50 mg, days 1-14 and Bev 15 mg/kg, every 3 weeks until disease progression occurred. RESULTS: In total, 39 patients were enrolled: after induction chemotherapy, the objective response was 74.3%. The median progression-free survival was 13.3 months, and the median overall survival was 33.2 months. Toxicity during maintenance treatment was mild. CONCLUSION: Maintenance with Cy and Bev may achieve encouraging results in terms of progression-free survival and overall survival in recurrent ovarian cancer patients.

Treatment of advanced oesophagogastric cancer with FOLFOX-4 regimen followed by leucovorin/bolus and continuous infusion 5-FU as maintenance chemotherapy in patients aged ≥ 75 years with impaired performance status.

OBJECTIVES: To evaluate the efficacy and safety of FOLFOX-4 combination chemotherapy, followed by leucovorin (LV)/bolus and continuous infusion 5-fluorouracil (5-FU) as maintenance chemotherapy in elderly (≥ 75 years) patients with advanced oesophagogastric cancer with impaired performance status (PS). MATERIALS AND METHODS: Patients with a PS score >1 were included in this study. PS evaluations were performed by a geriatrician and two medical oncologists. FOLFOX-4 consisted of oxaliplatin concurrently with LV/bolus and continuous infusion 5-FU every 2 weeks. After a maximum of six FOLFOX-4 cycles, patients with no evidence of disease progression received maintenance treatment with LV/bolus and continuous infusion 5-FU every 2 weeks until disease progression or unacceptable toxicity. RESULTS: Thirty-eight patients were enrolled in this study. Of these, 32 (84.2%) patients had a PS score of 2 and six (15.7%) patients had a PS score of 3. After completion of FOLFOX-4, 18 (47.3%) patients achieved a partial response and 14 (36.8%) patients had stable disease. Thirty-two patients (84.2%) received maintenance chemotherapy for a median of eight cycles (range one to 26 cycles). The 6-month disease-control rate was 47.3% [95% confidence interval (CI) 30.9-64.1]. The median progression-free survival was 5.9 months (95% CI 4.7-6.8) and the median overall survival was 9.6 months (95% CI 8.1-11.7). Grade 3 neutropenia occurred in six patients (15.7%), and Grade 3 anaemia and thrombocytopenia occurred in two patients (5.2%). CONCLUSION: FOLFOX-4 followed by LV/bolus and continuous infusion 5-FU as maintenance chemotherapy seems to be an active and well-tolerated first-line treatment strategy for elderly patients with advanced oesophagogastric cancer and impaired PS.

Role of chemotherapy in the treatment of metastatic castration-resistant prostate cancer patients who have progressed after abiraterone acetate.

Abiraterone acetate is a novel irreversible inhibitor of CYP17 that was recently approved for men with post-chemotherapy or chemo-naive castration-resistant prostate cancer. Unfortunately, this agent is not curative, and patients often ultimately develop resistance. However, men who progress after treatment with this new hormonal agent may be considered for another line of chemotherapy-based treatment. In 2004, docetaxel (D) and prednisone were found to improve survival compared with older regimens. More recently, cabazitaxel (C), a novel taxane chemotherapy, has been found to prolong survival in patients who exhibit disease progression during or after D chemotherapy. Here, we review the first clinical studies in which castration-resistant prostate cancer patients received chemotherapy with D or C after progression during abiraterone acetate treatment.