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3 Giugno 2009

SPECIALE ASCO 2009 – N. 4, 02/06/2009

Orlando, 2 giugno 2009

ASSEGNATO AL DR. CARLOS ARTEAGA IL PREMIO GIANNI BONADONNA
L’edizione 2009 del premio Gianni Bonadonna, istituito dall’ASCO nel 2007, ha visto vincitore il dr. Carlos L. Arteaga. Si tratta di un ricercatore che ha dedicato gran parte della sua attività professionale ai meccanismi patogenetici e alla terapia molecolare per il tumore del seno. Ha lavorato con Osborne a San Antonio e poi e’ diventato professore di medicina e oncologia alla Vanderbildt University. Ha approfondito lo studio dei fattori di crescita del tumore della mammella, individuandone il ruolo fondamentale nel promuovere la proliferazione, la capacita’ di invasione e metastatizzazione. Si tratta dell’EGRF, dell’IGF e di altri fattori verso i quali sono stati sviluppati e sono in corso di sperimentazione molti farmaci che potrebbero tornare utili al controllo del cancro della mammella.

PRESENTATA LA “ROADMAP” DELL’ASCO PER SUPERARE LE DISPARITÀ NELLA CURA DEL CANCRO
È stato pubblicato il policy statement dell’ASCO “Disparities in Cancer Care” che auspica una riforma complessiva del sistema per garantire pari accesso all’assistenza sanitaria per tutti i cittadini degli USA. L’ASCO è impegnata con l’amministrazione del presidente Obama per sviluppare possibili proposte ed ha individuato alcuni step che possono essere immediatamente adottati per migliorare l’assistenza per le minoranze e per chi non possiede un’assicurazione.
In particolare, la roadmap dell’ASCO richiede di:
– aumentare il numero di oncologi appartenenti a minoranze, per ampliare l’accesso alle cure e fornire una migliore assistenza, anche dal punto di vista della comunicazione e culturale, ai pazienti appartenenti a questi gruppi sociali.
– diversificare i trial clinici per includere più pazienti appartenenti alle minoranze
– fornire agli operatori e ai pazienti le informazioni necessarie per ridurre le disparità
“Solo con l’unione delle forze potremo raggiungere risultati significativi nella ricerca oncologica e nell’assistenza per tutti i pazienti – ha dichiarato Otis Brawley, co-chair dell’ ASCO’s Health Disparities Advisory Group – . Come? Con maggiori fondi e attenzioni al care, favorendo il supporto e il training di oncologi appartenenti a diverse popolazioni e rinforzando pesantemente la ricerca sulle disparità della sanità,”.

TUMORE GASTRICO AVANZATO: DATI POSITIVI CON TRASTUZUMAB
Nel 6-35% dei tumori dello stomaco e gastroesofagei si riscontra un’iperespressione del gene HER2. Il trastuzumab, un anticorpo monoclonale HER2 antagonista, ha dimostrato benefici di sopravvivenza in combinazione con la chemioterapia standard in pazienti con tumore del seno HER-2 positivo. Lo studio TOGA e’ il primo che ha indagato l’efficacy e la safety di trastuzumab in pazienti con carcinoma gastrico HER2 positivo. I risultati dimostrano che il trattamento con trastuzumab e’ superiore rispetto alla sola chemioterapia standard.

Abstract No: LBA4509
Efficacy results from the ToGA trial: A phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC).
Author(s): E. Van Cutsem, Y. Kang, H. Chung, L. Shen, A. Sawaki, F. Lordick, J. Hill, M. Lehle, A. Feyereislova, Y. Bang; University Hospital Gasthuisberg, Leuven, Belgium; Asan Medical Center, Seoul, Republic of Korea; Yonsei University College of Medicine , Seoul, Republic of Korea; Peking University School of Oncology, Beijing, China; Aichi Cancer Center, Nagoya, Japan; National Centre for Tumour Diseases, Heidelberg, Germany; Roche Products Pty Ltd, Dee Why, New South Wales, Australia; F. Hoffmann-La Roche Ltd, Basel, Switzerland; Seoul National University Hospital, Seoul, Republic of Korea
Background: Advanced GC is an incurable disease; new and less toxic treatments are needed. HER2 overexpression has been reported in 6-35% of stomach and gastroesophageal tumors. Trastuzumab (H; Herceptin), a monoclonal antibody against HER2, has shown survival benefits when given with CT in patients (pts) with HER2-positive early and metastatic breast cancer. The ToGA study is the first randomized, prospective, multicenter, phase III trial to study the efficacy and safety of H in HER2- positive GC. Methods: Pts with HER2-positive gastroesophageal and gastric adenocarcinoma (locally advanced, recurrent, or metastatic) were randomized to receive H+CT (5-fluorouracil or capecitabine and cisplatin) q3w for 6 cycles or CT alone. H was given until disease progression. The primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival, time to progression, duration of response, and safety. An interim analysis was planned at 75% of deaths and the Independent Data Monitoring Committee recommended releasing the data as the pre-specified boundary was exceeded and median follow-up of pts was 17.1 months. Results: Tumors from 3,807 pts were centrally tested for HER2 status: 22.1% were HER2 positive (abstract #4556). 594 pts were randomized 1:1 at sites in Europe, Latin America, and Asia. Baseline characteristics were well balanced across arms. Median OS was significantly improved with H+CT compared to CT alone: 13.5 vs. 11.1 months, respectively (p=0.0048; HR 0.74; 95% CI 0.60, 0.91). ORR was 47.3% in the H+CT arm and 34.5% in the CT arm (p=0.0017). Safety profiles were similar with no unexpected adverse events in the H+CT arm. There was no difference in symptomatic congestive heart failure between arms. Asymptomatic left ventricular ejection fraction decreases were reported in 4.6% of pts in the H+CT arm and 1.1% in the CT arm. Conclusions: This first randomized trial investigating anti-HER2 therapy in advanced GC showed that H+CT is superior to CT alone. The OS benefit indicates that H is a new, effective, and well-tolerated treatment for HER2-positive GC.

LO ZENZERO RIDUCE LA NAUSEA INDOTTA DALLA CHEMIOTERAPIA
Un ampio studio randomizzato ha dimostrato una significativa riduzione della nausea associata alla chemioterapia in pazienti che hanno assunto integratori allo zenzero in aggiunta ai farmaci antiemetici standard, con un beneficio pari al 73% nel primo giorno successivo alla chemioterapia in chi soffriva di questo effetto collaterale.
Lo studio multicentrico di fase II/III in doppio cieco ha coinvolto 644 pazienti. I ricercatori hanno evidenziato come lo zenzero riduca il modo significativo (P=0.003) la nausea vs il placebo. Julie L. Ryan dell’Università di Rochester ha presentato i dati durante la sessione dedicata ai pazienti.
Lo studio aveva arruolato malati con nausea durante la chemioterapia che avessero ancora di fronte almeno tre cicli di trattamento. A tutti è stato somministrato zenzero o placebo per 6 giorni prima e tre giorni dopo il ciclo di chemioterapia. Le conclusioni indicano che lo zenzero può significativamente migliorare la qualità di vita durante la chemioterapia.

Abstract 9511
Ginger for chemotherapy-related nausea in cancer patients: A URCC CCOP randomized, double-blind, placebo-controlled clinical trial of 644 cancer patients
Author(s): J. L. Ryan, C. Heckler, S. R. Dakhil, J. Kirshner, P. J. Flynn, J. T. Hickok, G. R. Morrow; University of Rochester Medical Center, Rochester, NY; Wichita CCOP, Witchita, KS; HOACNY CCOP, Syracuse, NY; Metro-MN CCOP, St. Louis Park, MN
Background: Despite the widespread use of antiemetics, post-chemotherapy nausea and vomiting continue to be reported by up to 70% of patients receiving chemotherapy. Ginger (Zingiber Officinale), an ancient spice, is used by practitioners worldwide to treat nausea and vomiting. We conducted a multi-site, phase II/III randomized, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for chemotherapy-related nausea in cancer patients at the University of Rochester-affiliated Community Clinical Oncology Program (CCOP) member sites. Methods: Cancer patients who experienced nausea following any chemotherapy cycle and were scheduled to receive at least three additional cycles were eligible. Patients were randomized into four arms: 1) placebo, 2) 0.5g ginger, 3) 1.0g ginger, or 4) 1.5g ginger. All patients received 5-HT3 receptor antagonist antiemetics on Day 1 of all cycles and took three 250mg capsules of ginger or placebo twice daily for six days starting three days before the first day of the next two cycles. Patients reported the severity of nausea during the morning, afternoon, evening, and night on a 7-point semantic rating scale (‘1’ = ‘Not at all Nauseated’ and ‘7’ = “Extremely Nauseated”) for Days 1-4 of each cycle. The goal was to determine if ginger was more effective than placebo in controlling chemotherapy-related nausea in participants given a 5-HT3 receptor antagonist antiemetic. Results: A total of 644 patients were accrued (90% female, mean age = 53). Breast (66%), alimentary (6.5%), and lung (6.1%) cancers were the most common cancer types. Analysis of covariance (ANCOVA) examined change in nausea in the four study arms on Day 1 of cycles 2 and 3. All doses of ginger significantly reduced nausea (p=0.003). The largest reduction in nausea occurred with 0.5g and 1.0g of ginger. Also, time of day had a significant effect on nausea (p<0.001) with a linear decrease over 24 hours for patients using ginger. Conclusions: Ginger supplementation at daily dose of 0.5g-1.0g significantly aids in reduction of nausea during the first day of chemotherapy. Supported by NCI PHS grants 1R25CA10618 and U10CA37420.

TRATTAMENTI TUMORALI E ANTIDEPRESSIVI
Fra gli effetti collaterali del tamoxifen vi sono le vampate, spesso gestite con gli antidepressivi Paxil e Prozac. Due nuovi studi hanno riportato risultati differenti su come questi farmaci possono modificare l’efficacia del tamoxifen.

Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors
R. E. Aubert, E. J. Stanek, J. Yao, J. R. Teagarden, M. Subar, R. S. Epstein, T. C. Skaar, Z. Desta, D. A. Flockhart
Background: Tamoxifen (TAM) is metabolized to its active form, endoxifen, by hepatic cytochrome P450 (CYP) 2D6. Diminished CYP2D6 function, both by genetic variation or concurrent use of pharmacologicinhibitors, can significantly reduce endoxifen plasma concentrations and may lead to reduced TAM effectiveness. Methods: We interrogated an integrated research database comprised of de-identified medical and pharmacy claims (Rx) data for 10.7 million U.S. health plan members to identify women with breast cancer (BrCa) new to TAM therapy in a 30-month period from 2003 to 2005, and investigated the risk of recurrent BrCa as a function of concurrent use of potent and moderate inhibitors of CYP2D6. Inclusion criteria were: greater than or equal to 24 months of follow-up data and adherence to TAM (medication possession ratio > 70%) over 2 years (N = 1298). Disease recurrence was defined by BrCa ICD-9 codes or CPT codes for mastectomy, lumpectomy, lymph node dissection, or radiation therapy occurring at least 6 months after the index TAM Rx. Two study groups were identified: TAM alone (N = 945) or TAM + a CYP2D6 inhibitor concomitantly (N = 353). BrCa recurrence rates were compared using Kaplan-Meier analysis with log-rank test, and univariate hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards model. Results:
The study groups were similar at baseline. Median age was 52 years (TAM) and 53 years (TAM + CYP2D6 inhibitor). Interventions performed in the TAM alone group included mastectomy in 54%, lumpectomy in 36%, and radiation therapy in 47%, and were 52%, 38%, 46%, respectively, in the TAM + CYP2D6 inhibitor group. Among women on a CYP2D6 inhibitor, the median duration of overlap with TAM was 255 days. Patients receiving TAM + a CYP2D6 inhibitor had a 2-year BrCa recurrence rate of 13.9% versus 7.5% in patients receiving TAM alone (HR 1.92, 95% CI 1.33-2.76, p < 0.001). Conclusions: Our
findings support the presence of a clinically significant drug interaction between TAM and known CYP2D6 inhibitors. This resulted in a significant 1.9 fold higher BrCa recurrence within 2 years of initiating TAM therapy. Disclosures: Ronald Aubert,,Employment or Leadership Position,Medco Health Solutions, Inc.Ronald Aubert,,Stock Ownership,Medco Health Solutions, Inc.Eric Stanek,,Stock Ownership,Medco Health Solutions, Inc.Eric Stanek,,Employment or Leadership Position,Medco Health Solutions, Inc.Jianying Yao,,Employment or Leadership Position,Medco Health Solutions, Inc.Jianying Yao,,Stock Ownership,Medco Health Solutions, Inc.J Teagarden,,Employment or Leadership Position,Medco Health Solutions, Inc.J Teagarden,,Stock Ownership,Medco Health Solutions, Inc.Milayna Subar,,Employment or Leadership Position,Medco Health Solutions, Inc.Milayna Subar,,Stock Ownership,Medco Health Solutions, Inc.Robert Epstein,,Stock Ownership,Medco Health Solutions, Inc.Robert Epstein,,Employment or Leadership Position,Medco Health Solutions, Inc.Todd Skaar,,Honoraria,Roche Molecular Systems, Inc.David Flockhart,,Consultant or Advisory Role,Roche Molecular DiagnosticsDavid Flockhart,,Consultant or Advisory Role,Medco Health Solutions, Inc.David Flockhart,,Consultant or Advisory Role,LabCorp

CRA509
Concomitant CYP2D6 inhibitor use and tamoxifen adherence in early stage breast cancer: A pharmacoepidemiological study

V. Dezentje, N. J. Van Blijderveen, H. Gelderblom, H. Putter, M. P. Van Herk – Sukel, M. K. Casparie, A. C. Egberts, J. W. Nortier, H. J. Guchelaar
Background: The use of cytochrome P450 2D6 inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Concomitant use of CYP2D6 inhibitors, such as the commonly prescribed selective serotonin reuptake inhibitors, as well as low tamoxifen adherence may negatively impact tamoxifen efficacy in breast cancer. The objectives were to relate concomitant CYP2D6 inhibitor use and tamoxifen adherence to breast cancer event free time (EFT). Methods: Data were used from PHARMO, a pharmacy database, PALGA, a nationwide pathology database and the Dutch Medical Register in the Netherlands. Breast cancer patients who were treated with tamoxifen as adjuvant therapy between 1994 and 2006 were included. A Cox proportional hazards model with a time-dependent definition for the CYP2D6 inhibitor exposure was used. Results: 1,990 breast cancer patients using tamoxifen were included, among whom 215 (10.8%) used a CYP2D6 inhibitor during tamoxifen treatment. No association between concomitant CYP2D6 inhibitor use and breast cancer recurrence was observed. Poor tamoxifen adherence was associated with lower EFT. Conclusions: This observational study did not show an association between concomitant CYP2D6 inhibitor use and breast cancer recurrence among patients treated with adjuvant tamoxifen. However, this study shows for the first time that poor tamoxifen adherence is associated with lower EFT.

SPECIALE QUALITY OF CARE
Fra gli studi presentati durante il meeting ne sono stati identificati alcuni particolarmente significativi per il miglioramento della qualità del care.

Prophylactic Creams and Antibiotics Reduce Severe Drug-Related Skin Rash: Giving colon cancer patients a combination of moisturizers, sunscreen, topical steroids and antibiotics before they receive the targeted therapy panitumumab reduced the incidence of a common, severe skin rash by more than half.

CRA 4027
Final STEPP results of prophylactic versus reactive skin toxicity (ST) treatment (tx) for panitumumab (pmab) related ST in patients (pts) with metastatic colorectal cancer (mCRC)
E. P. Mitchell, M. Lacouture, H. Shearer, N. Iannotti, B. Piperdi, M. Pillai, F. Xu, M. Yassine
Background: Pmab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is approved as monotherapy in the US for mCRC following disease progression (PD) and in the EU and Canada for tumors bearing wild-type (WT) KRAS. The most common toxicity with anti-EGFR inhibitors are ST. This study of pmab+ chemotherapy (CT) estimates the difference in the incidence of specific ≥ grade 2 ST of interest between pts receiving prophylactic (P) or reactive (S) skin tx. Methods: Pts had unresectable mCRC after PD with 1st-line fluoropyrimidine and oxaliplatin-based CT +/- bevacizumab. Pts received either pmab 6.0mg/kg/FOLFIRI Q2W or pmab 9 mg/kg/irinotecan Q3W. Within each stratum, pts were randomized 1:1 to either P ST tx 24 hrs before the 1st dose daily for 6 wks or R ST tx after ST occurred. Tx for ST included: moisturizers, sunscreen, topical steroid, and doxycycline. Efficacy and safety were evaluated by P vs R tx groups, KRAS status (mutant [MT] vs WT), and
chemotherapy status. Responses were assessed using modified RECIST with confirmation. Quality of life was assessed using the Dermatology Life Quality Index at screening, wks 2-7, and follow-up. Results: 95 pts were enrolled and randomized: 48 pts to P and 47 pts to R. During the 6 wk ST tx period, 29% of pts in the P group vs 62% of pts in the R group had protocol-specified ≥grade 2 ST. Of the 87 KRAS evaluable pts, 49 (56%) pts had WT KRAS and 38 (44%) pts had MT KRAS. Efficacy and safety are shown. Mean (SD) change in DLQI from baseline was 1.3 (2.6) for P and 4.2 (5.8) for R at wk 3 (when the median time to 1st ≥grade 2 ST was reached in the R group) and was 2.0 (2.8) for P and 2.6 (4.4) for R at wk 7. Conclusions: Prophylactic use of the skin tx regimen resulted in >50% reduction in the rate of specific ≥ grade 2 STs and improved QOL during the 6-week skin tx period vs R use. Numerical differences in favor of the P group were observed for all endpoints.

Disclosures: Edith Mitchell,,Consultant or Advisory Role,AmgenEdith Mitchell,,Research Funding,AmgenMario Lacouture,,Honoraria,AmgenMario Lacouture,,Research Funding,AmgenMario Lacouture,,Consultant or Advisory Role,AmgenBilal Piperdi,,Honoraria,AmgenFeng Xu,,Employment or Leadership Position,AmgenFeng Xu,,Stock Ownership,AmgenMohamed Yassine,,Employment or Leadership Position,AmgenMohamed Yassine,,Stock Ownership,Amgen

Low Rates of Screening among Childhood Cancer Survivors: Too few survivors of childhood cancer are getting recommended screenings for cancers of the breast, colon and skin, even though many have an elevated risk of these cancers.

CRA 6501
Cancer screening in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS)

P. C. Nathan, K. K. Ness, M. M. Hudson, M. Mahoney, J. S. Ford, W. Landier, G. Armstrong, T. Henderson, L. L. Robison, K. C. Oeffinger
Background: Childhood cancer survivors may develop a second malignant neoplasm (SMN) and require surveillance to detect new cancers. Methods: We surveyed survivors and siblings from the CCSS, a cohort study of patients who have survived ≥5 years after a diagnosis of childhood cancer from 1970-86. We assessed compliance with the American Cancer Society’s (ACS) guidelines for surveillance mammography, colonoscopy and PAP smears, and compared them to a matched population comparison group drawn from the 2003 National Health Interview Survey. Further, we examined compliance with the Children’s Oncology Group (COG) guidelines for more frequent colonoscopy, mammography and skin exams in survivors at high risk for cancers of the colon (≥30 Gy pelvic, abdominal or spinal radiation),breast (≥ 20 Gy breast radiation in females) or skin (any radiation). Proportions screened were compared between groups with adjusted generalized estimating equations or log-binomial regression models. Results: There were 8318 survivors (50.6% male, mean age at interview 31.2 ± 7.3 years), 2661 siblings and 8318 population controls. 141/829 (17.6%), 592/855 (70.4%) and 3362/3690 (92.6%) eligible survivors reported a Page 4 of 11 colonoscopy, mammogram, or PAP smear per ACS guidelines. Survivors were less likely than siblings (odds ratio [OR] 0.30; 95% confidence interval [CI] 0.18-0.49) and population controls (OR 0.63; CI 0.50-0.80) to have a colonoscopy, and less likely than siblings to have a PAP smear (risk ratio [RR] 0.98; CI 0.97-0.99). However, they were more likely than siblings (RR 1.14; CI 1.03-1.27) and population controls (RR 1.05; CI 1.01-1.10) to have a mammogram. Among survivors at increased risk for a SMN, only 92/809 (11.4%) reported a colonoscopy within the COG recommended 5-year period, 164/537 (30.5%) reported a mammogram within a 1-year period and 1288/4833 (26.7%) reported a skin exam. Care at a cancer center was associated with mammography (RR 1.91; 95% CI 1.02- 1.27) and skin exam (RR 1.55; 95% CI 1.22-196) in high-risk patients. Conclusions: Childhood cancer survivors are not screened adequately for SMN’s. Surveillance is very poor amongst those at highest risk for colon, breast, or skin cancer. Survivors and their physicians need education about the importance of surveillance.

Partial Breast Irradiation May Be as Effective as Conventional Radiation Therapy: Partial breast irradiation — a shorter, more targeted course of treatment than traditional radiation therapy — may offer the same benefits as conventional whole-breast radiation therapy for early-stage breast cancer with fewer side effects, but further study is necessary before the approach can be recommended for widespread use.

CRA 532
Partial breast irradiation or whole breast radiotherapy for early breast cancer: A meta-analysis of randomized controlled trials

A. Valachis, D. Mauri, N. P. Polyzos, D. Mavroudis, V. Georgoulias, G. Casazza
Background: The purpose of the study was to compare treatment outcomes in patients with breast cancer treated with partial breast irradiation and of those treated with whole breast-radiation therapy. Methods: We conducted a systematic review and meta-analysis of published. Randomized clinical trials comparing partial breast irradiation versus whole breast radiation therapy. Primary outcome was overall survival and secondary outcomes were loco-regional, distant and supraclavicular recurrences. Results: A search of the literature identified 3 trials with pooled total of 1140 patients. We found no statistically significant difference between partial and whole breast radiation arms associated with death (OR 0.912, 95% CI 0.674-1.234, p = 0.550), distant metastasis (OR 0.740, 95% CI, 0.506-1.082, p = 0.120), or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278- 7.202, p = 0.560). However, partial breast irradiation was statistically significantly associated with an increased risk of both local (pooled OR 2.150, 95% CI, 1.396-3.312; p = 0.001) and regional disease recurrences (pooled OR 3.430, 95% CI, 2.058-5.715; p < 0.0001) compared with whole breast-radiation. Conclusions: Partial breast irradiation does not jeopardize survival and may be used as an alternative to whole breast-radiation. Nevertheless, the issue of loco-regional recurrence needs to be further addressed.

IL CONGRESSO ASCO 2009 SI CHIUDE OGGI. L’APPUNTAMENTO PER IL 2010 È A CHICAGO DAL 4 ALL’8 GIUGNO

Fonte ASCO
Supplemento ad AIOM News
Editore Intermedia
Direttore responsabile Mauro Boldrini
TORNA INDIETRO