RPCI Physicians Share Research Results At American Society Of Clinical Oncology Meeting

Monday, June 6, 2011

BUFFALO, NY — Roughly 30,000 oncologists are convening in Chicago this weekend for the annual meeting of the American Society of Clinical Oncology (ASCO). Among those attendees are dozens of physicians from Roswell Park Comprehensive Cancer Center (Roswell Park) who will both share their most recent research with their colleagues and attend sessions by other researchers — a mutual exchange of ideas and information concerning the latest advances in cancer research and treatment.

Among the Roswell Park physicians invited to present data to their ASCO colleagues are the six lead authors whose abstracts are outlined here. These presentations include a study on an experimental regimen for solid tumors that was found to have therapeutic potential, final results of a phase I trial of a promising regimen for pancreatic cancer and a study that examined concordance with national practice guidelines for breast-cancer therapy as a measure of quality of care.

Efficacy in selected tumor types in a phase I study of the c-MET inhibitor ARQ 197 in combination with sorafenib

Abstract number: 3034

Lead author: Alex A. Adjei, MD, PhD, FACP, Senior Vice President of Clinical Research and Chair, Department of Medicine, Roswell Park

Session: Developmental Therapeutics - Experimental Therapeutics

Type: General Poster Session

Time: Monday June 6, 8 a.m. to 12 p.m. (McCormick Place Hall A)

Background: ARQ 197 (A) is a selective, oral, non-ATP competitive inhibitor of c-MET, a RTK implicated in tumor cell proliferation, invasion and metastasis, currently in phase II/III clinical trials. Based on preclinical synergy of A and sorafenib (S) in multiple cell lines, a phase I study was undertaken to define safety and RP2D of the A+S combination.

Results: To date, 54 pts (17 F/37 M; mean age: 61.4 yrs; 13 RCC, 8 HCC, 12 NSCLC, 8 melanoma, 7 BC, 6 others) have been treated, 5 at DL1 w/o DLT, 9 at DL2 with 2 DLTs in 1 pt (a Grade 3 fatigue and a Grade 3 dyspnoea) and 40 at the RP2D (extension cohort). Adverse events (AEs) considered related to one or both study drugs occurred in 45 (83.3%) pts with the most common ones (≥10%) being fatigue (35.2%), rash (31.5%), diarrhea (29.6%), anorexia (29.6%), nausea (18.5%), stomatitis (18.5%), alopecia (18.5%), hypophosphataemia (18.5%), vomiting (13.0%), pruritus (13.0%), hand-foot syndrome (11.1%) and lymphopenia (11.1%). Among 48 pts on extension cohorts, 37 (77.1%) were evaluable (defined as having at least one post-treatment CT scan) for efficacy.

Conclusions: The A+S combination therapy is well tolerated at full single-agent doses and RP2D has been identified. Preliminary evidence of anti-cancer activity has been observed, indicating that the combined inhibition of c-MET and angiogenic signalling demonstrates therapeutic potential.

A national evaluation of response and factors affecting response to neoadjuvant therapy in breast and rectal cancer

Abstract number: 6091

Lead author: Stephen Edge, MD, FACS, Alfiero Foundation Endowed Chair in Breast Oncology and Medical Director, Breast Center, Roswell Park

Session: Health Services Research

Type: General Poster Session

Time: Saturday June 4, 8 a.m. to 12 p.m. (McCormick Place Hall A)

Background: Neoadjuvant therapy (NAT) in breast (BC) and rectal cancer (RC) improves outcome and response to NAT is a prognostic factor. National use and response to NAT data outside clinical trials have not been reported because the cancer registry system does not record post-NAT “y” TNM stage. This study evaluated a modified registry system to collect pre-NAT and post-NAT “y” stage and define response rate and factors affecting NAT response.

Results: The study included 3,985 BC and 2,455 RC, comprising 44% of BC and 73% of RC treated by NAT in the NCDB. pCR occurred in 11.3% of BC and 11.2% of RC cases. Factors independently associated with pCR in BC were negative hormone receptors and clinically negative nodes before NAT; and in RC were resection of 5 or fewer lymph nodes, and treatment at NCI-designated cancer centers.

Conclusions: A modified registry data system allows identification of response to NAT. Nationwide rates of pCR in BC and RC showed pCR were lower than reported in clinical trials. Key factors associated with pCR in BC were negative hormone receptors and clinically negative nodes, and in RC limited node resection and treatment at NCI-designated centers.

Concordance with NCCN practice guidelines for local therapies as a measure of quality of care: Review of practice and identification of quality gaps

Abstract number: 6019

Lead author: Valerie Francescutti, MD, Clinical Fellow in Surgical Oncology, Roswell Park

Session: Health Services Research

Type: Poster Discussion Session

Time: Monday June 6, 2 p.m. to 6 p.m. (McCormick Place S403)

Discussion Time: Monday June 6, 5 p.m. to 6 p.m. (McCormick Place S404)

Background: Quality of cancer care may be assessed by determining concordance with guidelines. Guideline concordance alone may not be sufficient for determining quality as non-concordant (NC) care may be appropriate for individual cases. This study examined NC with local therapy (LT) breast cancer guidelines of the NCCN at Roswell Park Comprehensive Cancer Center.

Results: Among 1917 patient encounters there were 411 (21%) instances of NC care for LT; 52 patients had NC care for 2 guidelines. NC care for surgery accounted for 33% and radiation (RT) 67%. Most NC was MD recommended omission of axillary surgery and/or RT in older women with ER + breast cancer or DCIS. Database errors accounted for 5%. System failure was rare, accounting for 0.7%.

Conclusions: The majority of NC care was MD-recommended or patient-choice-related. Concordance reports allow objective assessment of quality of cancer care, and can be used for quality assurance. Cancer-center program review should be conducted to assure overall appropriateness of MD-recommend NC care.

Final results of a phase I study of the combination of a novel cell cycle inhibitor ON 01910.Na with gemcitabine in patients with advanced pancreatic and other solid tumors

Abstract number: 3101

Lead author: Wen Wee Ma, MBBS, Assistant Professor, Department of Medicine, Roswell Park

Session: Developmental Therapeutics - Experimental Therapeutics

Type: General Poster Session

Time: Monday June 6, 8 a.m. to 12 p.m. (McCormick Place Hall A)

Background: ON 01910.Na (ON) is a novel multitargeted inhibitor of several regulatory pathways including polo-like kinase 1 (Plk1) and PI-3 kinases, with synergistic preclinical activity when combined with gemcitabine (G; Jimeno et al, 2008, 2009), prompting a phase I clinical evaluation.

Results: Thirty-six pts (median age 61; median ECOG PS 1) received a median of 3 cycles (6 pts ongoing) at 5 dose levels: (G/ON mg/m2: 750/600 n=6; 1,000/600 n=5; 750/1,200 n=3; 1,000/1,200 n=3; 1,000/1,800 n=19). Only those toxicities that were expected from G were observed in patients treated with the combination, and included thrombocytopenia, neutropenia, elevated AST/ALT, nausea, vomiting, and fatigue. One DLT was documented (death at Day 18 at the 1,800 mg/m2 ON dose). Antitumor activity was seen in one G-pretreated Hodgkin lymphoma pt (PR), 2 ovarian cancer pts (1 G-pretreated with 50% decrease in CA125; 1 G-naïve with 50% decrease in CA125 and 12% tumor regression), one NSCLC pt (SD at 24 weeks) and one thymic cancer pt (PR at 32 weeks). Additionally, 18 advanced pancreatic cancer (PC) pts were enrolled. Tumor regression (including one confirmed PR in a G-pretreated pt) was noted in 7/13 evaluable pts and CA 19-9 decrease in 8/13 pts. Median progression-free survival was 19 weeks and overall survival 48 weeks at 1,200 and 1,800 mg/m2 ON doses (n=12) in the subset of 16 metastatic PC pts, 11 of whom were previously treated with G.

Conclusions: ON 01910.Na 1,800 mg/m2 and gemcitabine combination is well tolerated. Anti-tumor activity in G-pretreated pts with advanced PC provide the rationale for a phase II evaluation in metastatic PC pts. Final results will be presented and molecular data including PI3K mutation status.

Comparison of outcome in erythroleukemia patients treated with standard chemotherapy regimens or hypomethylating agents

Abstract number: 6630

Lead author: Carlos Vigil, MD, Assistant Professor, Leukemia Service, Department of Medicine, Roswell Park

Session: Leukemia, Myelodysplasia, and Transplantation

Type: General Poster Session

Time: Monday June 6, 1 p.m. to 5 p.m. (McCormick Place Hall A)

Background: Erythroleukemia is a rare form of acute leukemia often accompanied by unfavorable cytogenetics. Traditionally treated with a standard cytarabine-based induction regimen, median survival is poor (~8 months). Due to its rarity few studies have outcomes with alternate treatments. Hypomethylating drugs had demonstrated clinical activity in patients with poor risk myelodysplastic syndromes (MDS) with improved overall survival compared to best supportive care.

Results: The median age was 67 years (range, 38-84), 9 (27%) were females. Treatment was with azacytidine (AZA) in 12 (36%) and with decitabine (DAC) in 9 (27%) of the cases. 12 patients received therapy with cytarabine-based chemotherapy agents as induction. Cytogenetic analysis included diploid in 9, complex abnormalities in 19 and intermediate risk in 5. FLT3 mutations were absent in all 16 patients tested. Fourteen (67%) of the 21 patients treated with hypomethylating agents achieved a complete remission (CR) whereas five (42%) patients treated with induction chemotherapy; this was accompanied by complete cytogenetic remission in 14 of 16 evaluable patients. The median number of cycles to achieve CR was 3 (range, 2 to 4). After a median follow up of 8 months (range,1-58) the median overall survival time was 15.4 months (95%CI: 7.1 to 24.8) in those who receive hypomethylating agents versus 10 months (95%CI: 1.6 to 15.4) in those who did not (P=0.0322).

Conclusions:These results suggest that hypomethylating agents are highly active in patients with acute erythroleukemia and may extend survival compared to standard induction chemotherapy regimens. Benefit from high intensity therapy is limited, suggesting biological overlap with MDS.

Prospective structured smoking behavior assessment at diagnosis and long-term cancer survival

Abstract number:1557

Lead author: Graham Warren, MD, PhD, Assistant Professor, Department of Radiation Medicine, Roswell Park

Session: Cancer Prevention/Epidemiology

Type: General Poster Session

Time: Saturday June 4, 2 p.m. to 6 p.m. (McCormick Place Hall A)

Background: Evidence suggests that tobacco use decreases survival in cancer patients, but research to date is limited by a lack of standardized prospective tobacco use assessments. A standardized prospective assessment of smoking behavior was collected on patients from 1982-98. Survival data on patients completing the assessment within 30 days of cancer diagnosis were analyzed to assess the impact of smoking status at diagnosis on disease specific mortality (DSM) and overall mortality (OM).

Results: In 5185 patients (minimum 12 year follow-up), mean age at diagnosis was 59, 46% were male, 97% are white, 39% presented with local disease, 30% with regional disease, and 31% with distant disease. After adjustment for confounders, Cox proportional hazards analysis of the overall population demonstrates that current smoking significantly increased OM (HR 1.29 vs. former, 1.38 vs. never) and DSM (HR 1.23 vs. former, 1.18 vs. never). In men, Current smoking increased OM in lung (HR 1.43 vs. former), head/neck (HR 1.73 vs. former), and prostate cancer (HR 2.83 vs. never) and current smoking increased DSM in lung (HR 1.42 vs. former), head/neck (HR 1.9 vs. former), prostate (HR 2.17 vs. never), and leukemia (HR 1.77 vs. former, 1.81 vs. never). In women, current smoking increased OM in breast (HR 1.81 vs. former, 1.84 vs. never) and uterine (HR 1.88 vs. never) and current smoking increased DSM in breast (HR 1.69 vs. former, 1.73 vs. never). Current smoking status at diagnosis in several disease sites with small patient subsets achieved near significance for adverse outcome.

Conclusions: Current smoking at diagnosis is a significant adverse risk factor for long term OM and DSM in cancer patients. Tobacco use is an important variable that should be accurately accounted for in survival analyses for cancer patients.

The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Roswell Park, founded in 1898, was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit Roswell Park’s website at http://www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email AskRoswell@Roswellpark.org.

Editor’s note: These researchers and many other oncology experts from Roswell Park are available for interview, in person at the ASCO Annual Meeting or via phone/email. To connect with any expert from the comprehensive care team at Roswell Park, please contact media officer Annie Deck-Miller at annie.deck-miller@roswellpark.org or by phone at 716-602-5817.

Media Contact: 

Annie Deck-Miller, Senior Media Relations Manager
716-845-8593; annie.deck-miller@roswellpark.org