Slide Show: AACR Annual Meeting 2014

Slide 1: Subpopulation of Breast Cancer Patients Most Likely to Respond to PalbociclibPalbociclib in combination with letrozole nearly doubled progression-free survival compared with letrozole alone in first-line metastatic hormone receptor–positive, HER2-negative postmenopausal breast cancer patients. Progression-free survival was 20.2 months in the palbociclib arm compared with 10.2 months in the letrozole alone arm. The PALOMA-2 phase II trial randomized 165 patients 1:1 to two treatment arms. Progression-free survival was the primary endpoint of the study. Patients in the combination treatment arm had a 51% reduction in the risk of disease progression compared to patients treated with letrozole alone. Preliminary median overall survival was 37.5 months in the combination arm compared with 33 months in the control arm, not a statistically significant difference.[1]Slide 2: Novel Immunotherapy Shows Activity in Advanced MelanomaA novel two-component immunotherapy was shown to have efficacy and to be tolerable in a phase I trial of 31 advanced melanoma patients. Thus far, four patients had confirmed partial responses and multiple other patients had lesser responses that have not met the RECIST criteria for a partial response. Two of the partial responses have stayed on the therapies for more than 9 months, and one patient has had stable disease for more than 10 months. Dose-limiting toxicities included high-grade hypotension, rash, fever, and edema.[2]Slide 3: Antibody-Drug Conjugate Active in Three Types of MelanomaThe antibody-drug conjugate, DEDN6526A was shown to be safe and resulted in encouraging responses in cutaneous, mucosal, and ocular melanoma. Twelve of the nineteen patients in the phase I trial benefited from treatment, including four partial responses. Eight patients had stable disease. The agent consists of a cytotoxic chemotherapy molecule linked to an antibody against the endothelin B receptor (ETBR). Elevated levels of ETBR are present on the surface of about half of melanoma tumors.[3]Slide 4: Blocker of Epigenetic Activity Exhibits Efficacy in AML and Other Hematologic MalignanciesIn a phase I dose escalation trial, 7 of 38 patients with hematologic malignancies responded to treatment with OTX015, a small-molecule inhibitor of the BET-bromodomain proteins BRD2, 3, and 4. BET-bromodomain proteins create epigenetic modifications on genes that can turn gene expression on or off. Responses were seen in four acute myeloid leukemia (AML) patients, a patient with lymphoplasmacytic lymphoma, one patient with follicular lymphoma, and a patient with diffuse large B-cell lymphoma. Two of the AML patients had complete responses. Three of the seven patients are continuing to receive treatment.[4]Slide 5: FGFR Inhibitor Demonstrates Activity Against Solid TumorsIn a first-in-human trial, previously treated patients whose tumors harbored FGFR genetic alterations had tumor regressions upon treatment with BGJ398, an oral pan-FGFR inhibitor. Four patients with urothelial cell carcinoma had tumor reductions from 27% to 48%. A patient with FGFR1-amplified squamous cell carcinoma lung cancer had a complete response and another lung cancer patient had a partial response. A patient with cholangiocarcinoma and FGFR1-amplified breast cancer also had tumor regression. BGJ398 was shown to have a tolerable safety profile.[5]Slide 6: Liver Cancer Risk Reduced With Greater Coffee ConsumptionGreater coffee consumption results in lower risk of developing hepatocellular carcinoma, the most common type of liver cancer. Compared to those who consumed fewer than six cups of coffee per week, those who drank one to three cups per day had a 29% lower risk of developing hepatocellular carcinoma. Those who drank four or more cups of coffee per day had their risk reduced by 42% compared with those who drank six or fewer cups per week. The prospective study included almost 180,000 men and women of different ethnic backgrounds. The coffee consumption and liver cancer link was independent of age, gender, ethnicity, body mass index, smoking or alcohol consumption, diabetes, as well as hepatitis infection.[6]

References:

1. Finn RS, Crown JP, Lang I, et al. Final results of a randomized phase II study of PD 0332991, a cyclin-dependent kinase (CDK)-4/6 inhibitor, in combination with letrozole vs letrozole alone for first-line treatment of ER+/HER2-advanced breast cancer (PALOMA-1; TRIO-18). American Association for Cancer Research Annual Meeting 2014; April 5–9, 2014; San Diego. Abstr CT101.

2. Middleton M, Evans J, Steven N, et al. A Phase I study of IMCgp100: durable responses with a novel first-in-class immunotherapy for advanced melanoma. American Association for Cancer Research Annual Meeting 2014; April 5–9, 2014; San Diego. Abstr CT329.

3. Infante JR, Sandhu SK, McNeil CM, et al. A first-in-human phase I study of the safety and pharmacokinetic (PK) activity of DEDN6526A, an anti-endothelin B receptor (ETBR) antibody-drug conjugate (ADC), in patients with metastatic or unresectable melanoma. American Association for Cancer Research Annual Meeting 2014; April 5–9, 2014; San Diego. Abstr CT233.

4. Herait PE, Berthon C, Thieblemont C, et al. BET-bromodomain inhibitor OTX015 shows clinically meaningful activity at nontoxic doses: interim results of an ongoing phase I trial in hematologic malignancies. American Association for Cancer Research Annual Meeting 2014; April 5–9, 2014; San Diego. Abstr CT231.

5. Sequist LV, Cassier P, Varga A, et al. Phase I study of BGJ398, a selective pan-FGFR inhibitor in genetically preselected advanced solid tumors. American Association for Cancer Research Annual Meeting 2014; April 5–9, 2014; San Diego. Abstr CT326.

6. Setiawan VW, Wilkens LR, Hernandez BY, et al. Coffee intake reduces hepatocellular carcinoma risk: The Multiethnic Cohort. American Association for Cancer Research Annual Meeting 2014; April 5–9, 2014; San Diego. Abstr LB-281.