Memorial Sloan Kettering Cancer Center

About: Memorial Sloan Kettering Cancer Center is a healthcare organization based out in New York, New York, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 30293 authors who have published 65381 publications receiving 4462534 citations. The organization is also known as: MSKCC & New York Cancer Hospital.

Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer.

Abstract: Background Programmed death 1 (PD-1) blockade has clinical benefit in microsatellite-instability–high (MSI-H) or mismatch-repair–deficient (dMMR) tumors after previous therapy. The efficac...

Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study.

Abstract: Summary Background ALK fusion genes occur in a subset of non-small-cell lung cancers (NSCLCs). We assessed the tolerability and activity of crizotinib in patients with NSCLC who were prospectively identified to have an ALK fusion within the first-in-man phase 1 crizotinib study. Methods In this phase 1 study, patients with ALK -positive stage III or IV NSCLC received oral crizotinib 250 mg twice daily in 28-day cycles. Endpoints included tumour responses, duration of response, time to tumour response, progression-free survival (PFS), overall survival at 6 and 12 months, and determination of the safety and tolerability and characterisation of the plasma pharmacokinetic profile of crizotinib after oral administration. Responses were analysed in evaluable patients and PFS and safety were analysed in all patients. This study is registered with ClinicalTrials.gov, number NCT00585195. Findings Between Aug 27, 2008, and June 1, 2011, 149 ALK -positive patients were enrolled, 143 of whom were included in the response-evaluable population. 87 of 143 patients had an objective response (60·8%, 95% CI 52·3–68·9), including three complete responses and 84 partial responses. Median time to first documented objective response was 7·9 weeks (range 2·1–39·6) and median duration of response was 49·1 weeks (95% CI 39·3–75·4). The response rate seemed to be largely independent of age, sex, performance status, or line of treatment. Median PFS was 9·7 months (95% CI 7·7–12·8). Median overall survival data are not yet mature, but estimated overall survival at 6 and 12 months was 87·9% (95% CI 81·3–92·3) and 74·8% (66·4–81·5), respectively. 39 patients continued to receive crizotinib for more than 2 weeks after progression because of perceived ongoing clinical benefit from the drug (12 for at least 6 months from the time of their initial investigator-defined disease progression). Overall, 144 (97%) of 149 patients experienced treatment-related adverse events, which were mostly grade 1 or 2. The most common adverse events were visual effects, nausea, diarrhoea, constipation, vomiting, and peripheral oedema. The most common treatment-related grade 3 or 4 adverse events were neutropenia (n=9), raised alanine aminotransferase (n=6), hypophosphataemia (n=6), and lymphopenia (n=6). Interpretation Crizotinib is well tolerated with rapid, durable responses in patients with ALK -positive NSCLC. There seems to be potential for ongoing benefit after initial disease progression in this population, but a more formal definition of ongoing benefit in this context is needed. Funding Pfizer.

Sunitinib in Patients With Metastatic Renal Cell Carcinoma

Abstract: ContextCurrent treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients.ObjectiveTo confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy.Design, Setting, and PatientsOpen-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N = 106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy.InterventionRepeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle.Main Outcome MeasuresAssessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate (complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians (investigator assessment).ResultsAll 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months (95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively.ConclusionThe results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC.Trial Registrationclinicaltrials.gov Identifier: NCT00077974

Evaluating cell lines as tumour models by comparison of genomic profiles

Abstract: Cancer cell lines are frequently used as in vitro tumour models. Recent molecular profiles of hundreds of cell lines from The Cancer Cell Line Encyclopedia and thousands of tumour samples from the Cancer Genome Atlas now allow a systematic genomic comparison of cell lines and tumours. Here we analyse a panel of 47 ovarian cancer cell lines and identify those that have the highest genetic similarity to ovarian tumours. Our comparison of copy-number changes, mutations and mRNA expression profiles reveals pronounced differences in molecular profiles between commonly used ovarian cancer cell lines and high-grade serous ovarian cancer tumour samples. We identify several rarely used cell lines that more closely resemble cognate tumour profiles than commonly used cell lines, and we propose these lines as the most suitable models of ovarian cancer. Our results indicate that the gap between cell lines and tumours can be bridged by genomically informed choices of cell line models for all tumour types.