Publisher Correction: Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma.

In the version of this article originally published, there was an error in Fig. 2n. The top line of the HR comparison chart originally was Atezo + bev vs sun.

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma.

We describe results from IMmotion150, a randomized phase 2 study of atezolizumab (anti-PD-L1) alone or combined with bevacizumab (anti-VEGF) versus sunitinib in 305 patients with treatment-naive metastatic renal cell carcinoma. Co-primary endpoints were progression-free survival (PFS) in intent-to-treat and PD-L1+ populations. Intent-to-treat PFS hazard ratios for atezolizumab + bevacizumab or atezolizumab monotherapy versus sunitinib were 1.

Long-Term Response to Sunitinib Treatment in Metastatic Renal Cell Carcinoma: A Pooled Analysis of Clinical Trials.

Background: We characterized clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib who were long-term responders (LTRs), defined as patients having progression-free survival (PFS) > 18 months.

Patients And Methods: A retrospective analysis of data from 5714 patients with mRCC treated with sunitinib in 8 phase II/III clinical trials and the expanded access program. Duration on-study and objective response rate (ORR) were compared between LTRs and patients with PFS ≤ 18 months ("others").

Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.

Background: The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib.

Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.

Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010.

Sorafenib dose escalation in treatment-naïve patients with metastatic renal cell carcinoma: a non-randomised, open-label, Phase 2b study.

Objective: To assess the efficacy and safety of sorafenib dose escalation in metastatic renal cell carcinoma (mRCC).

Patients And Methods: Intra-patient dose escalation may enhance the clinical benefit of targeted anticancer agents in metastatic disease. In this non-randomised, open-label, Phase 2b study, treatment-naïve patients with mRCC were initially treated with the standard oral sorafenib dose [400 mg twice daily (BID)].

Sunitinib in the treatment of metastatic renal cell carcinoma.

Sunitinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that targets various receptors, including vascular endothelial growth factor receptors (VEGFRs). Sunitinib received approval in 2006 and became a standard treatment option in the first-line treatment of metastatic renal cell cancer (mRCC) after a phase III trial showed superiority compared with interferon alpha (IFN-α). Sunitinib has also shown activity in second-line treatment in several trials.

Long-term Safety of Sunitinib in Metastatic Renal Cell Carcinoma.

Background: Metastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive >2 yr, with chronic treatment sometimes extending to ≥6 yr.

Objective: To analyze long-term safety with sunitinib in mRCC patients.

Design, Setting, And Participants: Data were pooled from 5739 patients in nine trials, comprising seven phase II studies, a phase III study, and an expanded-access trial in various treatment settings (e.

Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma.

Introduction: Ipilimumab, a cytotoxic T lymphocyte-associated antigen-4 blocking antibody, has improved overall survival (OS) in metastatic melanoma in phase III trials. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a 'real world' population of patients treated with ipilimumab to identify markers for treatment benefit.

Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study.

Purpose: Preclinical data suggest that exposure to PARP inhibitors (PARPi) may compromise benefit to subsequent chemotherapy, particularly platinum-based regimens, in patients with BRCA1/2 mutation carrier ovarian cancer (PBMCOC), possibly through the acquisition of secondary BRCA1/2 mutations. The efficacy of chemotherapy in the PARPi-resistant setting was therefore investigated.

Experimental Design: We conducted a retrospective review of PBMCOC who received chemotherapy following disease progression on olaparib, administered at ≥200 mg twice daily for one month or more.

Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial.

Background: In a phase 3 trial comparing the efficacy and safety of axitinib versus sorafenib as second-line treatment for metastatic renal cell carcinoma, patients given axitinib had a longer progression-free survival (PFS). Here, we report overall survival and updated efficacy, quality of life, and safety results.

Methods: Eligible patients had clear cell metastatic renal cell carcinoma, progressive disease after one approved systemic treatment, and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.

Implications of BRCA1 and BRCA2 mutations for the efficacy of paclitaxel monotherapy in advanced ovarian cancer.

Introduction: Preclinical data suggest that BRCA1 and BRCA2 (BRCA1/2)-mutated ovarian cancers (BMOC) are exquisitely sensitive to platinum-salts, but resistant to microtubule-stabilizing anticancer agents. The clinical relevance of these preclinical data is unclear, since there are currently no published data on the efficacy of single-agent taxane chemotherapy in patients with BMOC. A retrospective study was undertaken to investigate the clinical effects of paclitaxel monotherapy in patients with BMOC.

Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies.

Purpose: Reovirus type 3 Dearing (RT3D) replicates preferentially in Ras-activated cancers. RT3D shows synergistic in vitro cytotoxicity in combination with platins and taxanes. The purpose of this phase I/II study was to assess RT3D combined with carboplatin/paclitaxel in patients with advanced cancers.

Cediranib monotherapy in patients with advanced renal cell carcinoma: results of a randomised phase II study.

Background: Cediranib is a highly potent vascular endothelial growth factor (VEGF) signalling inhibitor with activity against VEGF receptors 1, 2 and 3. This Phase II, randomised, double-blind, parallel-group study compared the efficacy of cediranib with placebo in patients with metastatic or recurrent clear cell renal cell carcinoma who had not previously received a VEGF signalling inhibitor.

Methods: Patients were randomised (3:1) to cediranib 45 mg/day or placebo.

Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer.

Context: Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear.

Objective: To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns.

Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.

Background: The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis. So far, no phase 3 randomised trials comparing the effectiveness of one targeted agent against another have been reported. We did a randomised phase 3 study comparing axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor (VEGF) receptors, with sorafenib, an approved VEGF receptor inhibitor, as second-line therapy in patients with metastatic renal cell cancer.

A HIF-regulated VHL-PTP1B-Src signaling axis identifies a therapeutic target in renal cell carcinoma.

Metastatic renal cell carcinoma (RCC) is a molecularly heterogeneous disease that is intrinsically resistant to chemotherapy and radiotherapy. Although therapies targeted to the molecules vascular endothelial growth factor and mammalian target of rapamycin have shown clinical effectiveness, their effects are variable and short-lived, underscoring the need for improved treatment strategies for RCC. Here, we used quantitative phosphoproteomics and immunohistochemical profiling of 346 RCC specimens and determined that Src kinase signaling is elevated in RCC cells that retain wild-type von Hippel-Lindau (VHL) protein expression.

Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib.

Background: Hypertension (HTN) is an on-target effect of the vascular endothelial growth factor pathway inhibitor, sunitinib. We evaluated the association of sunitinib-induced HTN with antitumor efficacy and HTN-associated adverse events in patients with metastatic renal cell carcinoma.

Methods: This retrospective analysis included pooled efficacy (n = 544) and safety (n = 4917) data from four studies of patients with metastatic renal cell carcinoma who were treated with sunitinib 50 mg/d administered on a 4-week-on 2-week-off schedule (schedule 4/2).

Genomic analysis reveals the molecular heterogeneity of ovarian clear cell carcinomas.

Purpose: Ovarian clear cell carcinomas (OCCC) are a drug-resistant and aggressive type of epithelial ovarian cancer. We analyzed the molecular genetic profiles of OCCCs to determine whether distinct genomic subgroups of OCCCs exist.

Experimental Design: Fifty pure primary OCCCs were subjected to high-resolution microarray-based comparative genomic hybridization (aCGH).

Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with severe renal impairment or on haemodialysis.

Objective: To further investigate the effect of sunitinib, which is currently a standard of care for the treatment of metastatic renal cell carcinoma (mRCC), in patients with severe renal impairment or those undergoing dialysis.

Patients And Methods: Clinical databases were used to identify all patients with mRCC treated with sunitinib in seven institutions internationally. Databases were searched to identify only those patients with an estimated glomerular filtration rate of < 30 mL/min/1.