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Medinews
9 Giugno 2010

SPECIALE ASCO 2010 – N. 4, 07/06/2010

Chicago, 7 giugno 2010

MANOVRA: FAZIO, SU BLOCCO TURN OVER POSSIBILE DISTINGUO ONCOLOGIA
La precondizione è lo stato dei conti economici, ma il ministro alla Salute, Ferruccio Fazio, non ha escluso che si possano concepire dei ‘distinguo’ per gli oncologi nell’ambito blocco del turn over per i dipendenti statali stabilito con la manovra finanziaria. “Tutto dovrà essere visto alla luce dei conti ma credo che ci potrà essere un distinguo per l’oncologia”. Il ministro ha così voluto tranquillizzare l’AIOM, che nei giorni scorsi ha manifestato preoccupazioni sul rischio che la manovra finanziaria possa abbassare la qualità di cura per i malati oncologici italiani. Fazio ha ricordato anche come “meccanismi di eccezione sui taglia alla spesa” siano già in essere in alcune regioni, tra le quali la Lombardia. Fazio ha quindi precisato che non si tratterebbe di “escludere tutti gli oncologi dal turn over, ma comunque di garantire in qualche maniera che le risorse per l’oncologia siano assolutamente adeguate”. In questo senso ha espresso il proprio “impegno personale” che si fonde con quello di rappresentante del Governo considerato che, ha aggiunto, “secondo lo stesso presidente Berlusconi la lotta contro il tumore e’ una priorità del Governo”, per la quale Fazio ha sottolineato l’intenzione di “fare in modo che questa manovra finanziaria non porti rallentamenti all’oncologia ma anzi vengano trovate risorse per dare nuovo stimolo alla ricerca, mettere a sistema i centri di eccellenza e promuovere l’attrazione di cervelli in Italia. Dobbiamo – ha concluso il ministro – anche esportare quanto facciamo e far diventare l’Italia nel Mediterraneo, in Europa e nel mondo un polo di ricerca oncologica”.

DIVENTARE MAMMA DOPO IL TUMORE, ITALIA LEADER DELLA RICERCA
La somministrazione di un analogo dell’ormone Lhrh mette al riparo le ovaie dai danni dei chemioterapici e salva la fertilita’. E’ questo il risultato dello studio coordinato e presentato all’ASCO dalla dr.ssa Lucia Del Mastro, il primo al mondo di questo tipo. «Abbiamo sperimentato una tecnica semplice – spiega l’oncologa dell’Istituto Tumori di Genova – che consiste nella somministrazione di un ormone, un analogo dell’Lhrh. Questo farmaco mette a riposo l’ovaio, riducendo così l’effetto tossico dei farmaci chemioterapici». Lo studio ha dimostrato che il farmaco riduce del 20% (dal 50 per cento al 30 per cento) il numero di donne che vanno incontro a una menopausa precoce, preservando quindi la fertilità. «Non sono poche oggi le donne che vanno incontro a un tumore al seno sotto i quarant’anni – aggiunge . – La percentuale si aggira attorno al 4% di tutti i casi, il che significa almeno 1.500 donne ogni anno in Italia. E, secondo i dati che abbiamo a disposizione, il 33% non ha figli». Lo studio ha coinvolto 16 centri per un totale di 280 pazienti, divisi in due gruppi, uno trattato e uno no, dimostrando l’efficacia del farmaco, ma lasciando ancora aperta la discussione sul suo meccanismo d’azione. «Ci possono essere due meccanismi – commenta la Del Mastro. – Il primo consiste in una riduzione della quantità di sangue che arriva all’ovaio e di conseguenza anche in una riduzione dei chemioterapici, presenti nel sangue, che possono raggiungere la ghiandola. Il seconda sta nel fatto che l’Lhrh blocca gli ormoni che fanno maturare i follicoli, preservandoli».

Role of LH-RH analog Triptorelin in preserving ovarian function during chemotherapy for early breast cancer patients: results of a multicenter phase III trial of Gruppo Italiano Mammella (GIM) group
L. Del Mastro, L. Boni, A. Michelotti, T. Gamucci, N. Olmeo, M. Giordano, C. Bighin, M. Venturini of behalf of GIM group, National Cancer Research Institute, Genoa , Italy

MEDULLOBLASTOMA, DA ITALIA CURE SU MISURA PER I BAMBINI
Parlano italiano le prime terapie su misura per i bambini colpiti dal medulloblastoma. Sono il risultato del più vasto studio al mondo in questo campo, durato 20 anni e presentato a Chicago. ”E’ una grande soddisfazione per l’oncologia italiana”, ha detto la coordinatrice della ricerca, Alba Brandes, del policlinico Sant’Orsola di Bologna. “Dopo che i pazienti vengono operati e il tumore rimosso chirurgicamente – ha proseguito la ricercatrice -, in tempi rapidissimi vengono analizzate le caratteristiche cliniche del tumore, in modo da valutare il rischio di eventuali ricadute. Nell’arco di due settimane – ha rilevato – si deve essere in grado di modulare la terapia a seconda del livello di rischio del paziente”: se il rischio e’ molto basso si può scegliere la sola radioterapia, se invece e’ elevato allora si combinano radioterapia e chemioterapia. Il vantaggio maggiore, ha concluso, ”e’ poter ridurre la somministrazione di una cura aggressiva come la chemioterapia quando non e’ necessaria, considerando che può provocare danni che si manifestano anche a distanza di tempo, e nello stesso tempo si può dare la dose massima del farmaco a chi ne ha bisogno”. La sopravvivenza a 5 e 10 anni è stata rispettivamente del 92 e del 65 percento nei pazienti a basso rischio, trattati con la sola radioterapia e del 58 e 45 percento in quelli ad alto rischio (radioterapia + chemioterapia).

Efficacy of tailored treatment for high- and low-risk medulloblastoma in adults: A large prospective phase II trial
A. A. Brandes, E. Franceschi, A. Tosoni, G. Frezza, R. Agati, A. Maestri, C. Ghimenton, V. Mazzocchi, L. Scopece, M. Ermani; Medical Oncology Department, Bellaria-Maggiore Hospital, Azienda USL of Bologna, Bologna, Italy; Radiotherapy Department, Bellaria-Maggiore Hospital, Azienda USL of Bologna, Bologna, Italy; Neuroradiology Department, Bellaria-Maggiore Hospital, Azienda USL of Bologna, Bologna, Italy; Verona Hospital, Verona, Italy; Neurosciences Department, Statistic and Informatic Unit, Azienda Ospedale-Università, Padova, Italy
J Clin Oncol 28:7s, 2010 (suppl; abstr 2003)

TESTA COLLO E POLMONE, PROMETTENTI I DATI DI UNA NUOVA PICCOLA MOLECOLA
Presentati all’ASCO nuovi dati di efficacia di BIBW2992 che fa parte di una nuova generazione di piccole molecole che hanno come bersaglio i recettori EGFR e HER2. La molecola agisce legandosi irreversibilmente ai recettori diversamente dagli inibitori della TKI di prima generazione.
Lo studio ha coinvolto 124 pazienti con tumore testa-collo metastatico. I risultati mostrano che BIBW2992 riduce le dimensioni del tumore nel 22% dei pazienti con carcinoma della testa e del collo, rispetto al 13% dei pazienti che hanno ricevuto cetuximab.
Sono stati inoltre presentati nuovi dati su BIBW2992 che ne riaffermano la significativa attività antitumorale nel NSCLC in presenza di mutazioni di EGFR. I dati dello studio LUX-LUNG 2 dimostrano che DCR = 94%, ORR = 62%. e PFS = 12 mesi.

BIBW 2992 versus cetuximab in patients with metastatic or recurrent head and neck cancer (SCCHN) after failure of platinum-containing therapy with a cross-over period for progressing patients: Preliminary results of a randomized, open-label phase II study.
T. Y. Seiwert, P. M. Clement, D. Cupissol, J. Del Campo, H. de Mont-Serrat, H. C. Thurm, A. S. Blackman, E. E. Cohen; The University of Chicago Medical Center, Chicago, IL; Department of General Medical Oncology, University Hospitals Leuven and Catholic University of Leuven, Leuven, Belgium; Centre Val d’Aurelle, Montpellier, France; Hospital Universitario Vall d’Hebron, Barcelona, Spain; Boehringer Ingelheim France S.A.S., Reims, France; Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT

A phase II study of BIBW 2992 in patients with adenocarcinoma of the lung and activating EGFR mutations (LUX-Lung 2)
C. Yang, J. Shih, W. Su, T. Hsia, C. Tsai, S. I. Ou, R. Calvo, X. J. Cong, M. Shahidi, V. A. Miller; National Taiwan University Hospital, Taipei, Taiwan; National Cheng Kung University Hospital, Tainan, Taiwan; China Medical University Hospital, Taichung, Taiwan; Taipei Veterans General Hospital, Taipei, Taiwan; Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA; Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT; Boehringer Ingelheim, Bracknell, United Kingdom; Memorial Sloan-Kettering Cancer Center, New York, NY

FOCUS TUMORE DEL POLMONE
Gli studi sul tumore del polmone che l’ASCO ha presentato con maggiore evidenza sono stati:

Drug Combination Increases Survival in Advanced Lung Cancer in the Elderly:
A Phase III study featured in ASCO’s plenary session shows that a combination of two commonly used chemotherapy drugs, paclitaxel (Taxol) and carboplatin, significantly increased overall and progression-free survival in patients age 70 or older with advanced non-small cell lung cancer (NSCLC) compared to the standard single-agent therapy. These findings suggest that older patients should be considered for the same aggressive therapy as younger patients.

Weekly paclitaxel combined with monthly carboplatin versus single agent therapy in patients aged 70 to 89: IFCT-0501 randomized phase III study in advanced non-small cell lung cancer (NSCLC).
E. A. Quoix, J. Oster, V. Westeel, E. Pichon, G. Zalcman, L. Baudrin, A. Lavole, J. Dauba, M. Lebitasy, B. J. Milleron, on behalf of IFCT

Background: Incidence of advanced NSCLC in the elderly is increasing. Specific trials for elderly are seldom and those patients are not optimally treated. Current recommendations are monotherapies with gemcitabine or vinorelbine.

Methods: French multicentric randomized phase III study in pts aged 70 to 89, PS 0-2 with advanced NSCLC not irradiable, comparing a 3- weekly single agent therapy (gemcitabine 1150 mg/m² or vinorelbine 30 mg/m², d1, d8 : arm A) with carboplatin AUC 6 every 4 weeks + paclitaxel 90 mg/m² (d1,8,15) doublet (arm B). Five cycles of single agent and 4 cycles of the doublet were to be given. Second-line in case of toxicity or progressive disease was fixed with erlotinib 150 mg/d. The main endpoint was overall survival.

Results: 451 pts were included from 04/2005 to 12/2009 by 60 centers. Males were 73.8%, median age was 77.2 years (range 70-89). PS was 0-1 in 73.6%. The 2 arms were well-balanced for pts characteristics. At time of 2nd planned intermediate analysis (after two-third of expected deaths, i.e.224), 451 pts were randomized, out of the 522 initially planned. The steering committee advice was to stop the inclusions. Overall survival of the 313 pts analysed at this time was significantly longer in arm B (median: 10.4 months, 95%CI: [8.2;15.0] vs 6.2 months, 95%CI: [5.3;7.5] for arm A, (HR=0.60, 95%CI : [0.46;0.78], p=0.0001). Median PFS was 6.3 months, 95%CI: [5.5;6.9] in arm B vs 3.2 months, 95%CI: [0.44;0.70] (HR=0.55, 95%CI: [0.44;0.70], p<0.0001). Grade 3-4 haematological toxicities were significantly more frequent in arm B (17.9% vs 54.1%). No significant difference was observed in early deaths (arm A : 23.7%, arm B : 16.6%). Survival, response and toxicity data for the whole series of 451 pts will be updated at time of the meeting.

Conclusions: Paclitaxel and carboplatin doublet provides a significantly longer survival in elderly pts with advanced NSCLC than current standard single agent therapy, with acceptable toxicity, making it a new treatment paradigm for PS 0-2 pts >=70 years.

Disclosures: Elisabeth Quoix, Consultant or Advisory Role, Lilly, roche, Honoraria, Lilly, Roche; Jean-Philippe Oster, Stock Ownership, Roche; Virginie Westeel, Honoraria, Lilly, Pierre Fabre Medicament, Other Remuneration, Lilly, Pierre Fabre Medicament, Roche; Eric Pichon, Honoraria, Roche, Other Remuneration, Roche; Gerard Zalcman, Consultant or Advisory Role, Lilly, Roche, Honoraria, Lilly, Roche, Research Funding, Roche; Armelle Lavole, Other Remuneration, Lilly; Marie-Paule Lebitasy, Consultant or Advisory Role, Lilly, roche, Honoraria, Lilly, Roche, Other Renumeration, Lilly, Roche, Research Funding, Lilly, Roche.

ALK Inhibitor Shows High Response Rate in Patients with Advanced NSCLC Harboring a Specific Gene Alteration:
A study featured in an ASCO plenary session shows that the majority of patients with advanced adenocarcinoma of the lung with a specific re-arrangement of the ALK gene responded to treatment with the investigational drug crizotinib (PF-02341066), which targets that genetic defect in the cancer cell. An estimated 5 percent of lung cancer patients have this ALK gene alteration.

Clinical activity of the oral ALK inhibitor, PF-02341066, in ALK positive patients with non-small cell lung cancer (NSCLC).
Y. Bang, E. L. Kwak, A. T. Shaw, D. R. Camidge, A. J. Iafrate, R. G. Maki, B. J. Solomon, S. I. Ou, R. Salgia, J. W. Clark

Background: PF-02341066 (PF-1066) is a selective, ATP-competitive, small molecule, orally bioavailable inhibitor of the ALK and MET/HGF receptor tyrosine kinases. EML4-ALK fusion oncogenes have been reported in approximately 4% of NSCLC. Patients with NSCLC harboring an ALK fusion were recruited into an expanded cohort at the recommended Phase 2 dose within the first-in-patient monotherapy trial of PF-1066.

Methods: Patients with ALK fusions, as determined by FISH using a break-apart probe to ALK, were enrolled into the expanded cohort irrespective of prior therapy. Treated brain metastases were allowed. PF-1066 was given orally at a dose of 250 mg BID. Responses were determined using RECIST with radiographic studies repeated every 8 weeks. The disease control rate (DCR) was determined based on the frequency of patients with RECIST CR, PR and stable disease at 8 weeks.

Results: To date, 76 ALK+ NSCLC patients have been treated. The median number of prior treatments was 3 (range, 0-7). Most patients had adenocarcinoma histology and were never or former smokers. Mean plasma Ctrough was 292 ng/ml, which was above the predicted efficacious concentration from preclinical models (120 ng/ml). The median t1/2 was ~53 hours. To date, 50 patients are evaluable for response; ORR is 64% and DCR 90%. The median progression-free survival is not yet mature. The median duration of treatment is 25.5+ weeks. Radiological responses typically were observed at the first or second restaging CT scan. Gastrointestinal toxicities, including nausea (55%) and vomiting (39%), were the most frequent adverse events.

Conclusions: The oral ALK inhibitor, PF-1066, demonstrated a high response rate in patients selected for ALK fusions and was associated with a good safety profile. A Phase 3 study has been initiated. This study supports the concept of molecular selection of NSCLC patients for appropriately designed treatment.

Disclosures: Yung-Jue Bang, Consultant or Advisory Role, Pfizer, Honoraria, Pfizer, Research Funding, Pfizer; Eunice Kwak, Research Funding, Pfizer; Alice Shaw, Honoraria, Pfizer, Research Funding, Pfizer; D. Camidge, Research Funding, Pfizer; A. Iafrate, Honoraria, Pfizer, Research Funding, Pfizer; Robert Maki, Research Funding, Pfizer; Benjamin Solomon, Research Funding, Peter MacCallum Cancer Center, Pfizer; Sai-Hong Ou, Research Funding, Pfizer; Ravi Salgia, Research Funding, Pfizer.

Selenium Doesn’t Prevent Second Lung Cancers:
A Phase III randomized, double-blind study of patients at risk for developing a second lung cancer found that selenium supplements did not prevent new lung cancers.

Abstract: CRA 7004
A phase III intergroup randomized double blind chemoprevention trial of selenium (Se) supplementation in resected stage I non small cell lung cancer (NSCLC).

D. D. Karp, S. J. Lee, G. L. Shaw Wright, D. H. Johnson, M. R. Johnston, G. E. Goodman, G. H. Clamon, G. S. Okawara, R. Marks, J. C. Ruckdeschel, MDACC Thoracic Chemoprevention Research Group.

Background: Selenium was reported to have possible lung cancer chemopreventive benefits based on a large skin cancer trial secondary observation. (JAMA 1996; 276: 1957-1963). Since that time, research continued to suggest that Se could decrease risk of second primary tumor (SPT) in persons with resected NSCLC. In 2007, a publication from another group suggested an increased association of Se with type 2 diabetes (Annals Int Med 147:217-223).

Methods: From Oct ’00 – Nov ’09, 6 Groups, led by ECOG, carried out a double blind placebo controlled trial using selenized yeast 200 micrograms daily in a 2:1 randomization vs. placebo for 48 mo in completely resected Stage I NSCLC. Participation was 6 -36 mo post-op and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, a negative chest x-ray and no other evidence of recurrence. Planned size of 1960 participants had been designed to detect a 40% decrease in SPTs with 80% power. Methylation studies of sputum and blood (S. Belinsky) add important biologic correlates to this project.

Results: Interim analysis occurred in Oct ’09 after 1561/1772 pts reached step 2 (completion of the 4 week (step 1) run-in period requiring at least 75% of the study drug to be taken). Endpoints included SPTs, recurrence, and toxicity. A total of 216 SPTs developed of which 84 (38.9%) were lung cancer. SPT (lung/overall) incidence was 1.36/3.66 per 100 person yrs for placebo vs 1.91/4.11 for Se (p=.150). 5 yr progression free survival was 78% for placebo vs 72% for Se. Study was stopped according to futility analysis. Grade 1 or 2 toxicity occurred in 38% of placebo and 39% Se. Grade 3 toxicity was 3% placebo vs <1% Se. Compliance was excellent (>95% at 2 yrs).

Conclusions: No increase in diabetes mellitus or skin cancer was detected. Se was safe but conferred no benefit over placebo. Methylation studies are continuing.

Disclosures: Daniel Karp, Research Funding, Pfizer.

Fonte ASCO
Supplemento ad AIOM News

Editore Intermedia
Direttore responsabile Mauro Boldrini
TORNA INDIETRO