i supplementi di TUMORI, a Journal of Experimental and Clinical Oncology
a publication of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Marco A. Pierotti, Director) an Official Journal of Società Italiana di Cancerologia (Riccardo Dolcetti, President)
Associazione Italiana di Oncologia Medica (Stefano Cascinu, President) Società Italiana di Chirurgia Oncologica (Alfredo Garofalo, President)
and Associazione Italiana di Radioterapia Oncologica (Giovanni Mandoliti, President)
EDITORIAL BOARD
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Epidemiology and Biometry Franco Berrino (Milano) Patrizia Boracchi (Milano) Paolo Bruzzi (Genova) Andrea Micheli (Milano) Ilaria Panzini (Rimini) Paolo Vineis (Torino) Clinical Pharmacology Maurizio D’Incalci (Milano) Cristiana Sessa (Bellinzona) Surgical Oncology
Vittorio A Bedini (Milano) Luca Cozzaglio (Milano) Luciano Di Martino (Cagliari) Roberto Doci (Milano)
Gabriella Ferrandina (Campobasso) Nicola Mozzillo (Napoli)
Medical Oncology
Giovanni Bernardo (Pavia) Francesco Boccardo (Genova) Sergio Bracarda (Arezzo) Roberto Buzzoni (Milano) Diego Cortinovis (Monza)
Maria Teresa Ionta (Monserrato, CA) Evaristo Maiello (San Giovanni
Rotondo, FG) Radiation Oncology Filippo Alongi (Milano) Stefano Magrini (Brescia) Mauro Palazzi (Milano) Umberto Ricardi (Torino) Elvio Russi (Cuneo) Vincenzo Valentini (Roma) Basic Research
Andrea Anichini (Milano)
Veronica Huber (Milano) Roberta Maestro (Aviano) Pathology
Carlo Capella (Varese) Vincenzo Eusebi (Bologna) Tumor Markers
and Diagnostic Procedures Emilio Bombardieri (Milano) Aldo Bono (Milano)
Maria Grazia Daidone (Milano) Palliative/Supportive Care & Cancer in the Elderly
Enrico Aitini (Mantova) Paolo Baili (Milano) Gianni Beretta (Milano) Oscar Bertetto (Torino) Carla Ripamonti (Milano) Fausto Roila (Perugia)
2013 Iscritto all’Unione Stampa Periodica Italiana
Alan Balmain (Glasgow) Mariano Barbacid (Princeton) Robert C Bast (Houston) Jacques Bernier (Bellinzona) Gianni Bonadonna (Milano) Vincent Castronovo (Liegi) Franco Cavalli (Bellinzona) Susan PC Cole (Kingston) Maria Ines Colnaghi (Milano) Paolo Comoglio (Torino) Carlo M Croce (Philadelphia) Riccardo Dalla Favera (New York) Mario De Lena (Bari)
Giuseppe Della Porta (Milano) Tommaso Dragani (Milano)
Suzanne Eccles (Belmont) Silvio Garattini (Milano)
Giuseppe Giaccone (Amsterdam) Geoffrey W Hanks (Bristol) Curtis Harris (Bethesda) Stephen B Howell (La Jolla) David Kerr (Oxford)
John M Kirkwood (Pittsburgh) Carlo La Vecchia (Milano) Ferdy J Lejeune (Lausanne) Alberto Mantovani (Milano) Ettore Marubini (Milano) Gordon J McVie (London)
Francesco M Marincola (Bethesda) Franco M Muggia (Los Angeles)
Pier Giorgio Natali (Roma) Lloyd J Old (New York) Marie Overgaard (Aarhus) Pier Giuseppe Pelicci (Perugia) Herbert M Pinedo (Amsterdam) Bruce Ponder (Cambridge) Vito Quaranta (La Jolla) Davide Schiffer (Torino)
Gilberto Schwartsmann (Porto Alegre) Rosella Silvestrini (Milano)
Paul Sugarbaker (Washington) Giovanni Tallini (New Haven) Giancarlo Vecchio (Napoli) Umberto Veronesi (Milano) Michael Zelefsky (New York) ADVISORY BOARD
i supplementi di TUMORI, a Journal of Experimental and Clinical Oncology
Volume 14, Number 1, October 2013
XV NatiONal CONgrEss Of MEdiCal ONCOlOgy
October 11-13, 2013: Milan, Italy
guest Editor stefano Cascinu
Medical Oncology, Università Politecnica delle Marche, Ancona
President, Italian Association of Medical Oncology (AIOM)
The Scientific Committee has chosen the papers on the basis of the originality of the research and the originality of the results.
The authors are responsible for the text and the translation.
i supplementi di TUMORI, a Journal of Experimental and Clinical Oncology
Volume 14, Number 1, October 2013 CONTENTS
(indexed in Current Contents/Life Sciences, EMBASE/Excerpta Medica, Elsevier BIOBASE/Current Awareness in Biological Sciences)
XV NatioNal coNgress of medical oNcology
October 11-13, 2013: Milan, Italy
abstracts
s1 Plenary session s4 Session A
colorectal cancer s28 Session B
Head and neck tumours s36 Session C
melanoma s42 Session D
Neuroendocrine tumours s45 Session E
continuous care in the cancer patient s66 Session F
gynaecological tumours s70 Session G
genitourinary tumours s92 Session H
lung cancer s116 Session L
Breast cancer s154 Session M
sarcomas s159 Session N
lymphomas and myeloma s161 Session P
Primary and secondary brain tumours s164 Session Q
gastrointestinal tumours (colorectal excluded) s182 Session R
Psychological and psychosocial aspects, rehabilitation problems s189 Session S
miscellanea s194 Session T
oncology nursing s203 Author index
Please, note that abstracts marked with an asterisk (*) are Oral communications.
15th National Congress of Medical Oncology October 11-13, 2013: Milan, Italy
guest Editor stefano Cascinu Medical Oncology
Università Politecnica delle Marche, Ancona
15th National Congress of Medical Oncology October 11-13, 2013: Milan, Italy
guest Editor stefano Cascinu Medical Oncology
Università Politecnica delle Marche, Ancona
dear Colleagues,
on behalf of the Board of directors and of the scientific Committee, it is a great plea- sure for me to introduce the proceedings of the XV National Congress of our association.
as usually, the abstracts have been published in a special issue of “tumori”, the official Journal of aiOM. By reading them, there are at least two aspects of satisfaction.
the first one is the increasing number of abstracts. it seems to suggest not only the in- terest for the Congress but also a diffuse research activity in italy. this is not limited to a specific geographic area but it involves all the country.
the second aspect is the role of young oncologists. Many and many young oncologists are coauthors of the abstracts and several are first authors. this is probably the most rele- vant indication at least in my mind: there is a present for aiOM but there will be also a fu- ture.
as you can realize by reading this issue, all topics of medical oncology has been cov- ered. these topics, including prevention, screening, translational research, simultaneous care, ethics and multidisciplinary approaches, will be debated in several educational and scientific sessions. We would like to highlight as simultaneous care and multidisciplinary approach are relevant parts of the program of the meeting. as medical oncologists, clini- cians involved in the care of the patients, we have to keep in our mind that “research”
does not mean to forget the daily activity in the ward as well as the ability to answer the patients’ daily needs. Nevertheless, at the same way, we must remember that a research activity improves the care of cancer patients in our Units. the ability to conjugate these two aspects is the only way to improve the chance of cure for our patients.
finally, i’d like to thank the scientific Committee and all the reviewers for the invalu- able work along last months and i hope that all of you can enjoy the meeting and it could be the occasion of sharing knowledge, and experiences by providing an enrichment in our skills.
the Board of directors for the years 2011-2013 includes:
• stefano Cascinu (President)
• Carmine Pinto (Secretary)
• stefania gori (Treasurer)
• Massimo aglietta
• giuseppe altavilla
• Editta Baldini
• giovanni Bernardo
• saverio Cinieri
• fabio Puglisi
• Pierosandro tagliaferri
• giuseppe tonini
We are looking forward to seeing you in Milan.
Prof. stefano Cascinu (President of the Congress)
This abstracts book will be available on-line and will also be freely available to all visitors to the following website from October 14th, 2013 (http://www.aiom.it)
XV NATIONAL CONGRESS MEDICAL ONCOLOGy PLENARy SESSION S1
Plenary session
1* folfoxiri/bevAcizumAb (bev) versus folfiri/bev As first-line treAtment in unresectAble metAstAtic colorectAl
cAncer (mcrc) pAtients: results of the phAse iii tribe triAl by gono group
Cremolini C.1, Loupakis F.1, Masi G.1, Lonardi S.2, Zagonel V.2, Salvatore L.1, Trenta P.3, Tomasello G.4, Ronzoni M.5, Ciuffreda L.6, Zaniboni A.7, Tonini G.8, Buonadonna A.9, Valsuani C.10, Chiara S.11, Carlomagno C.12, Boni C.13, Marcucci L.14, Boni L.15, Falcone A.1
1Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa; 2Oncologia Medica 1, Istituto Oncologico Veneto, Padova;
3DH Oncologico, Policlinico Umberto I, Roma; 4Istituti Ospita- lieri di Cremona, Cremona; 5Dipartimento di Oncologia Medica, Istituto Scientifico San Raffaele, Milano; 6Oncologia Medica, Ospedale Molinette, Torino; 7Casa di Cura Poliambulanza, Bre- scia; 8Dipartimento di Oncologia Medica, Università Campus Biomedico, Roma; 9Dipartimento di Oncologia Medica, Istituto Nazionale Tumori, Aviano; 10UO Oncologia Medica, Ospedale Versilia, Lido di Camaiore; 11Unità di Oncologia Medica, Istituto Nazionale per la Ricerca sul Cancro, Genova; 12Università di Napoli Federico II, Napoli; 13Oncologia Medica, Arcispedale Santa Maria Nuova, Reggio Emilia; 14Oncologia Medica, Ospe- dale Lotti, Pontedera; 15Istituto Toscano Tumori, Firenze
background. Doublets plus bev are a standard option for the first-line treatment of mCRC. First-line FOLFOXIRI demonstrat- ed superior RR, PFS and OS compared to FOLFIRI. A phase II study of FOLFOXIRI/bev showed promising activity and man- ageable toxicities. The objective of the TRIBE trial was to con- firm the superiority of FOLFOXIRI vs FOLFIRI when bev is added to chemotherapy (CT).
patients and methods. Eligibility criteria included: measur- able and unresectable mCRC, age 18-75 years, no prior CT for advanced disease. Patients were randomized to either FOLFIRI/bev (arm A) or FOLFOXIRI/bev (arm B). Both treat- ments were administered for a maximum of 12 cycles followed by 5FU/bev until progression. Primary endpoint was PFS.
results. Between July 2008 and May 2011, 508 pts were ran- domized. Patients characteristics were (arm A/arm B): median age 60/61, ECOG PS 1-2 11%/10%, synchronous metastases 81%/79%, multiple sites of disease 74%/70%, liver-only disease 18%/23%, prior adjuvant (adj) 13%/13%. At a median follow-up of 32.3 mos 439 pts progressed and 286 died. FOLFOXIRI/bev significantly increased PFS (median 9.7 vs 12.1 mos, HR 0.77 [0.64-0.93] p = 0.006). A more consistent effect of FOL- FOXIRI/bev was reported in no prior adj (HR 0.70 [0.58-0.86]) compared to prior adj group (HR 1.30 [0.75-2.25]), with a signif- icant p for interaction (p = 0.039). Subgroup analyses based on baseline characteristics (PS, site of primary, liver only disease, resection of primary, Kohne score) did not evidence significant interactions between treatment and analyzed factors. Response rate (RECIST) was also significantly improved (53% vs 65%, p
= 0.006). FOLFOXIRI/bev did not increase the R0 secondary re- section rate in the ITT population (12% vs 15%, p = 0.327), or in the liver-only subgroup (28% vs 32%, p = 0.823). OS results will be presented.
conclusions. FOLFOXIRI/bev, compared to FOLFIRI/bev, significantly increases PFS and response rate. Subgroup analysis
suggests a possible interaction between prior adj CT and PFS benefit. Secondary resection rate does not differ between treat- ment arms.
2* A rAndomized multicentre phAse iii study compAring weekly vs every 3 weeks
cArboplAtin (c) plus pAclitAxel (p) in pAtients with AdvAnced ovAriAn cAncer (Aoc): mito-7 (multicentre itAliAn triAls in ovAriAn cAncer) - engot-ov-10 (europeAn network of gynAecologicAl oncologicAl triAl groups) - gcig (gynecologic cAncer intergroup) triAl
Pignata S.1, Scambia G.2, Lauria R.3, Raspagliesi F.4, Benedetti Panici P.5, Cormio G.6, Katsaros D.7, Sorio R.8, Cavazzini G.9, Ferrandina G.10, Breda E.11, Murgia V.12, Sacco C.13, Asensio Sierra N.M.14, Cinieri S.15, Pisano C.1, Salutari V.2, Lorusso D.4, Di Maio M.1, Gallo C.16, Perrone F.1
1Istituto Nazionale Tumori, Fondazione “G. Pascale”, Napoli;
2Università Cattolica del Sacro Cuore, Roma; 3Università Fede- rico II, Napoli; 4Fondazione IRCCS, Istituto Nazionale Tumori, Milano; 5Università “Sapienza”, Roma; 6Università di Bari, Ba- ri; 7Ospedale “S. Anna”, Università di Torino, Torino; 8Centro di Riferimento Oncologico, Aviano; 9Ospedale “C. Poma”, Manto- va; 10Università Cattolica del Sacro Cuore, Campobasso;
11Ospedale Fatebenefratelli, Roma; 12Ospedale Santa Chiara, Trento; 13Ospedale Universitario “S. Maria della Misericordia”, Udine; 14Arcispedale “S. Maria Nuova”, IRCCS, Reggio Emilia;
15Ospedale “A. Perrino”, Brindisi; 16Seconda Università, Napoli
background. CP administered every 3 weeks (3w) is standard 1st line chemotherapy for AOC patients. In a JGOG phase 3 trial, weekly (w) P combined with 3w C prolonged PFS and OS. MI- TO-7 is an academic phase 3 study, comparing 3w vs w CP (ClinicalTrials.gov NCT00660842).
methods. AOC chemonaïve pts, stage IC-IV, aged 75, ECOG PS = 2, were randomized to 3wCP (C AUC6 + P 175 mg/m², d1q21) for 6 cycles or to wCP (C AUC2 + P 60 mg/m²) for 18 administrations. Coprimary endpoints were PFS and quality of life (QoL), measured by FACT-O and FACT/GOG-Ntx. With 80% power in detecting HR of 0.75, 2-sided a = 0.05, 383 events were needed for PFS analysis. The arms were compared with a log-rank test and in a Cox model adjusted by stage, PS, residual disease, age and size of institution, following intention-to-treat (ITT). QoL was measured at baseline and weekly for 9 wks: pri- mary measure of QoL was FACT-O Trial Outcome Index (TOI).
Interaction between arm and QoL time was tested in a linear mixed model. Toxicity was coded by NCI-CTCAE v3.0.
results. Between 2008 and 2012, 822 pts were enrolled by MITO, MANGO and GINECO, and 808 pts were eligible for ITT analysis. Median age was 60; stage III (66%) and IV (18%) were prevalent. As of March 18, 2013, with median follow-up 20 months, 410 events were recorded for PFS analysis. Median PFS was 18.8 months with wCP and 16.5 months with 3wCP (HR 0.88, 95%CI 0.72-1.06, p = 0.18). Lack of significant difference was confirmed (HR 0.86, 95% CI 0.71-1.05) in Cox model. For FACT-O TOI, FACT-O and FACT/GOG-Ntx, QoL course in the first 9 weeks was significantly different between arms (p
<0.0001). With 3wCP, QoL scores clearly worsened after each chemotherapy course (weeks 1, 4, 7), whilst with wCP, after a small and transient worsening at week 1, scores remained stable.
A significant treatment : time interaction favouring wCP (p
<0.0001) was observed also for neurotoxicity subscale. Weekly CP produced significantly less G ≥3 neutropenia (50% vs 39%), febrile neutropenia (3% vs <1%), G ≥3 thrombocytopenia (7% vs 1%), G ≥3 renal toxicity (2% vs 0%), G2 hair loss (58% vs 28%) and G ≥2 neuropathy (16% vs 6%).
conclusions. Compared to CP every 3 weeks, weekly CP did not significantly prolong PFS, but was associated with better QoL and lower toxicity. Given the observed confidence interval of PFS, MITO7 QoL and toxicity data further support a weekly schedule as 1stline treatment of AOC in clinical practice.
3* A lArge prospective itAliAn populAtion study (project of emiliA-romAgnA region in neuro-oncology; perno) in newly diAgnosed gbm pAtients: outcome AnAlysis And
correlAtions with mgmt methylAtion stAtus in the elderly populAtion
Franceschi E.1, Tosoni A.1, Poggi R.1, Depenni R.2, Mucciarini C.3, Faedi M.4, Dazzi C.5, Urbini B.6, Cavanna L.7, Marcello N.8, Crisi G.9, Michiara M.10, Pasini G.11, Bartolotti M.1, Palleschi D.1, Albani F.12, Ermani M.13, Baruzzi A.12, Brandes A.1
1Department of Medical Oncology, Bellaria Hospital, Azienda USL, Bologna; 2Oncology, Haematology and Respiratory Dis- eases Department, University Hospital of Modena, Modena; 3De- partment of Oncology and Haematology, Ramazzini Hospital, Carpi; 4Department of Medical Oncology, Istituto Scientifico Ro- magnolo per lo Studio e la Cura dei Tumori (IRST-IRCCS), Cese- na; 5Department of Oncology and Hematology, General Hospi- tal, Ravenna; 6Clinical Oncology Unit, S. Anna University Hos- pital, Ferrara; 7Department of Oncology and Haematology, On- cology Unit, Azienda Ospedaliera Guglielmo da Saliceto, Pia- cenza; 8Neurology Department, Arcispedale Santa Maria Nuova, Reggio Emilia; 9Department of Neuroradiology, Azienda Ospe- daliero-Universitaria, Parma; 10Medical Oncology Unit, Univer- sity Hospital, Parma; 11Department of Medical Oncology, Infer- mi Hospital, Rimini; 12IRCCS Istituto delle Scienze Neuro- logiche, Department of Neurological Sciences, University of Bologna, Bologna; 13Neurosciences Department, Statistics and Informatics Unit, Azienda Ospedale-Università, Padova
background. The role of temozolomide concurrent with and adjuvant to radiotherapy (RT/TMZ) in elderly pts with GBM re- mains unclear. We therefore evaluated the efficacy of this approach in pts >70 years in the context of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), the first Italian prospective observational population-based study in neuro-oncology.
methods. The criteria for selecting pts enrolled in the PERNO study were: age >70 years; PS 0-3; histologically confirmed GBM; post-operative radiotherapy after surgery; residence in the Emilia Romagna region. Data were collected prospectively.
results. Patients accrual, started on January 1, 2009, was closed, as planned, on December 31, 2010. In the pts enrolled (N
= 53), median overall survival (mOS) was 11.1 months (95% CI 8.8-13.5); survival rates at 1-, 2- and 3-year were 41.5% (95% CI 28.2- 54.8%), 15.2% (95% CI 4.8-25.6%) and 6.1% (95% CI 0- 15.9%), respectively. Twenty-eight pts received RT/TMZ, and 25 pts RT alone. mOS was 11.6 months (95% CI 8.6-14.6) following RT/TMZ and 9.3 months (95% CI 8.1-10.6) following RT alone.
mOS for pts with MGMT methylated status (N = 17) was 13.5
S2 PLENARy SESSION XV NATIONAL CONGRESS MEDICAL ONCOLOGy
months (95% CI 7.7-19.2), being 17.2 months (95% CI 11.5- 22.9) in those treated with RT/TMZ (N = 6) and 8.8 months (95% CI 2-15.6) in those treated with RT alone (N = 11, p = 0.09). Elderly pts with MGMT unmethylated status (N = 25) had a mOS of 8.5 months (95% CI 6-11, p = 0.014), being 8.5 months (95% CI 2.3-14.7) in pts treated with RT/TMZ (N =10), and 8 months (95% CI 3-12.9) in those treated with RT (N = 15, p = 0.55).
conclusions. RT/TMZ appears to be more effective in pro- longing the mOS of elderly pts in those with MGMT methylation status (17.2 vs 8.5 months), and seem to perform better than TMZ alone, for which mOS was 9.7 months in the Nordic phase III trial. These findings underline the value of the ongoing ran- domized EORTC 26062-22061/NCIC CE.6 phase III comparing RT/TMZ with short course RT alone.
4* A phAse ii-iii study compAring concomitAnt chemorAdiotherApy (crt) vs cetuximAb/rt (cet/rt) with or without induction tpf in locAlly AdvAnced heAd And neck squAmous cell cArcinomA (lAscchn). toxicity And efficAcy results (nct01086826)
Ghi M.G.1, Paccagnella A.2, Ferrari D.3, Foa P.3, Cossu Rocca M.4, Verri E.4, Maiello E.5, Azzarello G.6, D’Ambrosio C.7, Casanova C.8, Guaraldi M.9, Mantovani G.10, Rossetto C.11, Bonetti A.12, Cipani T.13, Crinò L.14, Koussis H.15, Pieri G.16, Gava A.17, Floriani I.18
1Ospedale SS Giovanni e Paolo, Venezia; 2Divisione di Oncolo- gia Medica, Venezia; 3Oncologia Medica, Ospedale San Paolo, Milano; 4Istituto Europeo di Oncologia, Milano; 5IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo; 6Dipartimento di Scienze Mediche, Unità Operativa di Oncologia, Mirano; 7Di- partimento di Oncologia, Modena; 8Divisione di Oncologia Me- dica, Azienda USL, Ravenna; 9Divisione di Oncologia Medica, Policlinico S. Orsola-Malpighi, Bologna; 10Divisione di Oncolo- gia Medica, Università di Cagliari, Cagliari; 11Divisione di On- cologia, Azienda Ospedaliero-Universitaria, Udine; 12Divisione di Oncologia, Ospedale Mater Salutis, Legnago; 13Divisione di Oncologia, Ospedale Niguarda Ca’ Granda, Milano; 14U.O. On- cologia Medica, Ospedale S. Maria della Misericordia, Perugia;
15IRCCS Istituto Oncologico Veneto-IOV, Padova; 16Dipartimen- to di Oncologia Medica, Ospedali Riuniti di Trieste, Trieste;
17Dipartimento di Radioterapia, Ospedale Ca’ Fondello, Treviso;
18Dipartimento di Oncologia, Istituto di Ricerche Farmacologi- che Mario Negri, Milano
background. This is the first phase III study directly compar- ing CRT vs CET/RT in LASCCHN. Primary endpoints of this study were to compare: 1) overall survival (OS) of induction vs no induction arms; 2) grade 3-4 in-field toxicity of CRT vs CET/RT. Here we present toxicity results (one of the primary endpoints) and efficacy results (secondary endpoint) for the two concomitant treatments (CRT vs CET/RT), irrespective of induc- tion chemotherapy.
methods. Untreated patients with LASCCHN of the oral cav- ity, oropharynx, hypopharynx, stage III-IV, ECOG PS 0, were randomized to a 2x2 factorial design. Patients were randomized from the beginning to one of the four treatment options: Arm A1:
CRT (2 cycles of cisplatin/5fluorouracil concomitant to standard RT fractionation); Arm A2: CET/RT; Arm B1: 3 cycles of TPF followed by the same CRT; Arm B2: 3 cycles of TPF followed by CET/RT.
xv NATIONAl CONGRESS MEdICAl ONCOlOGy PlENARy SESSION S3 Results. A total of 421 patients were randomized: 261 re-
ceived CRT (131 Arm A1+ 130 Arm B1) and 160 received CET/RT (80 Arm A2+ 80 Arm B2). No significant differences were observed in patients’ characteristics distribution. At a medi- an follow-up of 35 months, a total of 186 deaths occurred (204 required for final OS analysis). Median PSF was 20.9 mos in CRT arm and 20.7 in CET/RT arm (p = NS). Median OS was 39.5 mos in CRT arm vs 38.2 mos in CET/RT arm (p = NS). In field-toxicities are shown in Table 1.
Conclusions. No significant differences in grade 3-4 in-field toxicities and efficacy were observed between CRT and CET/RT.
The number of required events has not yet been reached for the OS evaluation of induction vs no induction arms.
4* - Table 1
CRT CET/RT p value
N = 233 (%) N = 158 (%) Mucositis + skin
in-field, per pts
Any grade 192 (82) 125 (79) 0.415
Grade 3-4 102 (44) 74 (47) 0.551
Mucositis
Any grade 182 (78) 114 (72) 0.177
Grade 3-4 89 (38) 57 (36) 0.670
Skin in-field
Any grade 134 (58) 105 (66) 0.075
Grade 3-4 32 (14) 31 (19.6) 0.120
S4 SESSION A XV NATIONAL CONGRESS MEDICAL ONCOLOGy
Session A • Colorectal cancer
A1* bevAcizumAb beyond progression in metAstAtic colorectAl cAncer pAtients receiving A first-line treAtment contAining bevAcizumAb: updAte of bebyp triAl by gono
Salvatore L.1, Masi G.1, Loupakis F.1, Cremolini C.1, Schirripa M.1, Fornaro L.2, Miraglio E.3, Granetto C.3, Antonuzzo L.4, Giommoni E.4, Lucchesi S.5, Barbara C.6, Boni C.7, Banzi M.7, Sonaglio C.8, Garbarino D.8, Valsuani C.9, Bonetti A.10, Boni L.1, Falcone A.1
1UO Oncologia Medica 2 Universitaria, Azienda Ospedaliero- Universitaria Pisana, Pisa; 2Oncologia AUSL 2, Lucca; 3UO On- cologia Medica, Azienda Sanitaria Ospedaliera S. Croce e Carle, Cuneo; 4UO Oncologia Medica, Azienda Ospedaliero-Universi- taria Careggi, Firenze; 5UO Oncologia Medica, Presidio Ospe- daliero Felice Lotti, Pontedera; 6UO Oncologia Medica, AUSL 6, Livorno; 7UO Oncologia Medica, Nuova Azienda Ospedaliera, Reggio Emilia; 8UO Oncologia Medica, IRCSS Azienda Ospeda- liero-Universitaria S. Martino-IST, Genova; 9UO Oncologia Me- dica, Ospedale Versilia, Lido di Camaiore; 10UO Oncologia Me- dica, Ospedale Mater Salutis, Legnago; 11Centro Coordinamento Sperimentazioni Cliniche, Istituto Toscano Tumori, Firenze
background. The continuation of bevacizumab (BV) with sec- ond-line chemotherapy (CT) beyond progression in patients (pts) who received the anti-VEGF monoclonal antibody (moAb) as part of first-line treatment can improve the outcome. Recently, results of the AIO/AMG ML18147 study demonstrated an improved over- all survival (OS) by continuing BV beyond progression.
patients and method. This phase III study randomized pts with unresectable metastatic colorectal cancer (mCRC) and mea- surable disease according to RECIST criteria, treated in first-line with BV plus fluoropyrimidine, FOLFIRI, FOLFOX or FOL- FOXIRI, to receive a second-line CT with mFOLFOX6 or FOLFIRI (depending on first-line CT) with or without BV. The primary endpoint was progression-free survival (PFS). To detect a HR for PFS of 0.70 with an a and b error of 0.05 and 0.20 re- spectively, assuming an accrual time of 24 months and a follow- up of 12 months, we planned to randomize 262 pts.
results. Considering the results of the AIO/AMG ML18147 trial that showed an improved OS with the prosecution of BV be- yond progression, the study accrual was stopped prematurely. A total of 185 pts were randomized and 184 pts were included in the ITT analysis (1 pt randomized in error). Patients characteris- tics for arm A (CT alone) and arm B (CT plus BV) were the fol- lowing: number 92/92, gender M75%-F25%/M57%-F43%, me- dian age 66 (38-75)/62 (38-75) years, PS = 0 82%/82%, multiple site of disease 76%/77%, liver-only disease 15%/13%. At the first analysis (median follow-up of 18 months) the study met its primary endpoint by demonstrating an improvement in PFS in the BV containing arm. We updated results and at a median fol- low-up of 30.4 months the improvement in PFS for the experi- mental arm was confirmed with a median PFS of 5.0 months for arm A and 6.7 months for arm B (HR = 0.66; 95% CI 0.49-0.89;
unstratified p = 0.0065). Subgroup analyses showed a consistent benefit in all the subgroups including gender and first-line PFS.
Response rates (RECIST) were 18% and 21% (p = 0.71) in arm A and B, respectively. Toxicity profile was consistent with previ- ously reported data. The OS data are still immature, with 70 events in arm A and 66 in arm B and the HR is 0.75 (95% CI 0.54-1.06) in favour of experimental arm (unstratified p = 0.11).
conclusions. This study demonstrates an improvement in PFS by continuing BV in second-line in pts who had received CT+BV in first-line. Updated survival results will be presented at the congress.
A2* confirmAtory AnAlysis of nrAs mutAtion As poor prognostic indicAtor And predictor of resistAnce to Anti-egfr monoclonAl Antibodies (Anti-egfrs) in metAstAtic colorectAl cAncer (mcrc) pAtients
Schirripa M.1, Loupakis F.2, Cremolini C.2, Morvillo M.2, Bergamo F.3, Zoratto F.4, Salvatore L.2, Antoniotti C.2, Marmorino F.2, Sensi E.5, Lupi C.5, Fontanini G.5, De Gregorio V.2, Giannini R.5, Basolo F.5, Masi G.2, Falcone A.2
1A.O. Universitaria, Pisa; 2U.O. Oncologia Medica 2, Azienda Ospedaliero-Universitaria Pisana, Pisa; 3Istituto Oncologico Ve- neto, IRCCS, Padova; 4Dipartimento di Scienze Medico-Chirur- giche e Biotecnologie, Università “Sapienza” di Roma; U.O.C.
Oncologia Universitaria,Ospedale I.C.O.T., Latina; 5Divisione di Anatomia Patologica, Dipartimento di Chirurgia, Università di Pisa, Pisa
background. NRAS belongs to RAS family. NRAS muta- tions are mutually exclusive with KRAS and BRAF mutations and contribute to the activation of Ras/Raf/MAPK pathway. Pre- vious experiences evaluated the prognostic/predictive role of NRAS mutations suggesting a poorer prognosis and resistance to anti-EGFRs for NRAS mutant (mut) mCRC patients. The aim of the present study was to confirm such preliminary findings in a large cohort of mCRC patients.
material and methods. Data on KRAS (codons 12, 13 and 61) and BRAF-V600E mutational status of mCRC pts referred to our pathology from ‘09 to ‘12 were collected. NRAS mutational status (codons 12, 13 and 61) was evaluated in KRAS and BRAF wt patients. OS was calculated from date of diagnosis of metasta- tic disease. Data on response and PFS according to RECIST were collected for NRASmut irinotecan-refractory pts treated with an- ti-EGFRs ± irinotecan.
results. 774 mCRC pts were included. KRAS/BRAF muta- tions were found in 384 (50%)/69 (9%) cases. NRAS was mut in 47 (15%) out of 318 KRAS and BRAF wt patients. NRAS mut pts had significantly shorter OS in comparison to KRAS-BRAF- NRAS wt pts (HR = 0.60 [0.29-0.99] p = 0.045). BRAF mut pts had significantly worse OS in comparison to NRAS mut pts (HR
= 1.75 [1.073-2.87] p = 0.03). No difference was observed be- tween NRAS mut and KRAS mut pts (HR = 0.86 [0.51-1.43] p = 0.61). Eighteen pts out of 47 NRAS mut pts received anti-EGFRs in advanced lines. Eight pts (7 cetuximab-based, 1 panitumumab monotherapy) were evaluable according to RECIST criteria and therefore eligible for the present analysis. None of them respond- ed and only 1 SD was observed. Pooling our results with avail- able data on anti-EGFRs’ activity in NRASmut pts in advanced lines of treatment (De Roock, 2010; Peeters, 2013; Andrè, 2012), only 1 response is described out of 35 treated pts (2.9%).
conclusions. Our data demonstrate that NRAS mutations have a relevant incidence in KRAS and BRAF wt mCRC pa- tients. Present results are consistent with previous experiences and confirm that NRAS mutations affect prognosis of mCRC pa- tients and predict lack of response to anti-EGFRs. Further in- sights into NRAS mut mCRC biology and prospective validation are warranted.
XV NATIONAL CONGRESS MEDICAL ONCOLOGy SESSION A S5 A3* phArmAcogenetic profiling for toxicity
of oxAliplAtin And fluoropyrimidines. finAl report from An AncillAry protocol to the toscA triAl
Ruzzo A.1, Galli Fabio2, Giacomini E.1, Floriani I.2, Rulli E.2, Galli Francesca2, Lonardi S.3, Ronzoni M.4, Massidda B.5, Pella N.6, Mucciarini C.7, Labianca R.8, Veltri E.9, Sozzi P.10, Barni S.11, Pasquini E.12, Sobrero A.13, Frontini L.14,
Magnani M.1, Graziano F.15
1Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino, Urbino; 2Laboratorio di Ricerca Clinica, Dipartimento di Oncologia IRCCS, Istituto di Ricerche Farmacologiche “Ma- rio Negri”, Milano; 3IOV-IRCCS, Padova; 4Ospedale San Raf- faele, Milano; 5Azienda Ospedaliera Universitaria di Cagliari, Cagliari; 6Azienda Ospedaliera Universitaria S. Maria della Mi- sericordia, Udine; 7Ospedale “B. Ramazzini”, Carpi; 8Azienda Ospedaliera “Ospedali Riuniti”, Bergamo; 9Ospedale di Gaeta ASL, Latina; 10Ospedale degli Infermi, Biella; 11Ospedale “Trevi- glio-Caravaggio”, Treviglio; 12Azienda Ospedaliera Ospedale
“Cervesi”, Cattolica; 13Azienda Ospedaliera “Ospedale San Martino”, Genova; 14Fondazione GISCAD, Milano; 15Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro
background. In the TOSCA trial, an ancillary pharmacoge- netic study was conducted for a prospective association analysis of known genetic variants with toxicity, useful for optimizing the management of patients during adjuvant chemotherapy. Current evidence is often limited to retrospective and not powered stud- ies.
methods. TOSCA is a multicentre, randomized, phase III study conducted in radically resected high risk stage II and III colon cancer patients treated with 6 or 3 months of either FOL- FOX-4 or XELOX. We analyzed 17 polymorphisms in 11 genes related to 5-fluorouracil/oxaliplatin pathways, detoxification, transport and DNA repair (TS, MTHFR, ERCC1, XRCC1, XR- CC3, XPD, GSTT1, GSTP1, GSTM1, ABCC1, ABCC2) and in- vestigated their association with the maximum grade of toxicity (MGT) and the time to toxicity (TTT) as recorded for its maxi- mum grade. Sample size calculation was based on an expected prevalence of an unfavourable genotype profiling of at least 30%.
105 grade 3-4 (also 2 for neurotoxicity) selected toxicity events (approximately 440 patients) allowed to detect an odds ratio (OR) of at least 2.0 associated to the group with unfavourable genotypes with a power of 90% and a I -type error of 5%, for a bilateral test.
results. 534 patients were enrolled (195 in the 6-month FOL- FOX-4 arm, 194 in the 3-month FOLFOX-4 arm, 69 in the 6- month XELOX arm, 76 in the 3-month XELOX arm). Regarding the proportion of stage II-III patients, the study sample is repre- sentative of main study sample, according to the two options of adjuvant chemotherapy and treatment duration (3 versus 6 months). 517 patients were analyzed. For neurotoxicity and neu- tropenia we have observed the required events. The XRCC3 TT (rs# 861539) genotype was protective for neurotoxicity (TTT) with a 0.58 HR (95% CI = 0.35-0.96; p = .03), the GST-T1/M1 null/+ genotype was associated with risk of neurotoxicity (TTT) with a 2.46 HR (95% CI = 1.07-5.65; p = .03). The GST-T1/M1 +/+ genotype was associated with protection risk of netropenia (MGT) with a 0.51 HR (95% CI = 0.27-0.95; p = .03).
conclusions. The results of this study are useful for improv- ing the monitoring of potentially cured colon cancer patients un- dergoing adjuvant chemotherapy. It will be evaluated whether the genetic profiles, for which a statistically significant association in
terms of MGT/TTT was observed, will determine different dose intensity and then possible different clinical outcomes.
A4* results of observer study on skin toxicity And cetuximAb bAsed regimen compliAnce in first-line chemotherApy of metAstAtic colorectAl cAncer (mcrc)
Rosati G.1, Lolli I.R.2, Di Fabio F.3, Signorelli C.4, Ciuffreda L.5, Ferrari D.6, Tumolo S.7, Rosti G.8, Tralongo P.9, Ferrara R.10, Alabiso O.11, Chiara S.12, Ianniello P.13, Di Costanzo F.14, Frassoldati A.15, Iacono C.16, Clerico M.17, Pavesi L.18, Bernardo A.18, Pinto C.3
1Medical Oncology, S. Carlo Hospital, Potenza; 2Medical Oncol- ogy, IRCCS Saverio De Bellis, Castellana Grotte (BA); 3Medical Oncology, S. Orsola-Malpighi Hospital, Bologna; 4Medical On- cology, Belcolle Hospital, Viterbo; 5Medical Oncology, Molinette Hospital, Torino; 6Medical Oncology, S. Paolo Hospital, Milano;
7Medical Oncology, S. Maria Degli Angeli Hospital, Pordenone;
8Medical Oncology, S. Maria Di Ca’ Foncello Hospital, Treviso;
9Medical Oncology, Di Maria Hospital, Avola (SR); 10Medical Oncology, Dimiccoli Hospital, Barletta; 11Medical Oncology, Maggiore della Carità Hospital, Novara; 12Medical Oncology, National Cancer Institute, Genoa; 13Medical Oncology, S. Anna and S. Sebastiano Hospital, Caserta; 14Medical Oncology, Careggi Hospital, Firenze; 15Medical Oncology, S. Anna Hospi- tal, Ferrara; 16Medical Oncology, Maria Paternò Hospital, Ra- gusa; 17Medical Oncology, Degli Infermi Hospital, Biella;
18Medical Oncology, Maugeri Foundation, Pavia
background. Cetuximab significantly improves efficacy when added to chemotherapy in patients (pts) with KRAS wild- type metastatic colorectal cancer (mCRC). The ObservEr Study evaluated the quality of life, skin toxicity management and treat- ment compliance of cetuximab based regimens in first-line chemotherapy of mCRC patients.
methods. ObservEr is a non-interventional, multicenter, prospective study. Primary endpoint is change in QoL during first-line treatment, with focus on the impact of dermatological toxicity. QoL (Dermatology Life Quality Index/DLQI and EORTC QLQ C30) is assessed at baseline and weekly for the first 8 weeks of treatment, then at every evaluation visit until PD or withdrawal. Secondary endpoints are efficacy, rate of liver metastases resection, incidence of serious adverse events.
results. Between April 2011 and November 2012, 29 Italian centers enrolled 233 pts, with 229 evaluable patients. Patients characteristics were: 154 (67.2%) males, 75 (32.8%) females;
median age 65 (39-81) years; PS ECOG 0-1 100%; potentially resectable liver metastases 64 (27.9%); irinotecan regimens 150 (63.4%), oxaliplatin regimens 69 (30.2%), other regimens 10 (4.3%). Median interval between request and result of KRAS test was 10 days. Prophylactic skin treatment with vitamin K1 cream was used in 164 (71.6%) pts, reactive treatment included vitamin K1 in 60 (26.0%). Grade 1-2 skin toxicity was observed in 147 (64.2%) pts, and grade 3 in 30 (13.1%); no grade 4 was detected.
No significant difference in grade 3 skin toxicity was observed between males vs females (14.9 vs 9.3%; p = 0.238), age <60 vs
≥60 years (19.2 vs 10.3%; p = 0.062), irinotecan vs oxaliplatin regimens (11.3 vs 17.4; p = 0.563), 5-fluouracil vs capecitabine (14.8 vs 9.6; p = 0.697); prophylactic vs reactive treatment (14.6 vs 10.0%; p = 0.626). Cetuximab compliance ≥70% of dose was reached in 212 (92.6%) pts, with permanent discontinuation of the drug related to toxicity in 12 (5.2%) pts. Median duration of
S6 SESSION A XV NATIONAL CONGRESS MEDICAL ONCOLOGy
cetuximab treatment in the 153/229 pts who already stopped was 15 weeks (range 1-60.1 weeks).
conclusions. These results show that the introduction of the Italian skin toxicity management recommendations and K1 cream in the prophylactic or reactive treatment reduce the inci- dence of grade 3 skin toxicity with improvement of cetuximab compliance.
A5* is it useful to wAit longer thAn conventionAl 6-8 weeks between pre-
operAtive chemorAdiotherApy And surgery in locAlly AdvAnced rectAl cAncer? A systemAtic review with metA-AnAlysis
Fontana A.1, Petrelli F.2, Coinu A.2, Riboldi V.3, Cabiddu M.2, Russo A.1, Ghilardi M.2, De Stefani A.4, Quadri F.1, Bruschieri L.3, Lonati V.2, Dallera P.1, Borgonovo K.5, Zabbialini G.1, Cremonesi M.2, Sarti E.3, Sgroi G.1, Barni S.2
1Department of Surgery, Oncological and General Surgery Unit,
2Department of Oncology, Medical Oncology Unit, 3Department of Oncology, Radiotherapy Unit, 4Department of Medical Oncol- ogy, Radiotherapy Unit, 5Department of Medical Oncology, On- cology Unit, Azienda Ospedaliera Treviglio-Caravaggio, Tre- viglio
objective. This review considers the influence of the time lapse between the end of pre-operative chemoradiotherapy (CTRT) and surgery on the pathologic complete response (pCR) in locally advanced rectal cancer, in order to evaluate possible benefits of a time-interval longer than conventional 6-8 weeks.
summary background data. The standard of care of locally advanced rectal cancer is pre-operative, long course (5-fluo- rouracil-based) CTRT. A period of 6-8 weeks from CTRT is cur- rently considered the most effective timing to perform surgery.
methods. A systematic research, concerning prospective or retrospective studies reporting oncological results of pre-opera- tive CTRT in locally advanced rectal cancer, was carried out on PubMed, Embase, ISI Web of Science and The Cochrane library (CENTRAL). The primary endpoint, reported as relative risk (RR), was the rate of pCR. Secondary endpoints were overall survival (OS), disease-free survival (DFS), R0 resection rates, sphincter preservations and wound/anastomotic complications. A meta-analysis was performed, using the fixed- or random-effects model, with Review Manager 5.1.
results. We have found thirteen trials including 3,584 pa- tients. An interval longer than 6-8 weeks from the end of pre-op- erative CTRT and surgery significantly improved pCR (RR 1.42, 95% CI 1.2-1.69; p <0.0001) that increased from 13.9 to 19.5%
in longer interval group. No significant differences for OS, DFS, R0 resection rates, sphincter preservation and complication rates were observed.
conclusions. A time-interval from the end of pre-operative CTRT and surgery, longer than the 6-8 weeks period, increases by 6% the rate of pCR in rectal cancer, with a similar outcome and complication rates. These results have to be validated prospectively in a randomized trial.
A6 prognostic vAlue of incidentAl
betAblockers use in metAstAtic colorectAl cAncer pAtients receiving first-line
treAtment. An updAte
Del Prete M., Giampieri R., Scartozzi M., Faloppi L., Bian- coni M., Bittoni A., Cascinu S.
AOU Ospedali Riuniti, Università Politecnica delle Marche, An- cona
background. Preclinical and retrospective studies suggested an antitumor activity for the incidental use of anti-hypertensive betablockers in various tumour types, reducing metastasis, tumor recurrence and increasing survival. Data regarding colorectal cancer are lacking. We tried to assess the correlation between the incidental use of betablockers and clinical outcome in colorectal cancer patients receiving first-line therapy.
material and methods. 250 colorectal cancer patients, treat- ed with first-line chemotherapy alone (135 patients) and with chemotherapy plus bevacizumab (115 patients), were analysed for progression-free survival and overall survival, using the Ka- plan-Meier method. A p value <0.05 was considered for statisti- cal significance. Patients were stratified for betablockers use, age, sex, site of metastases, previous adjuvant chemotherapy and ECOG performance status.
results. Thirty-one patients (12%) were on treatment with betablockers at the time of first-line therapy: 22 (16%) in the chemotherapy alone group and 9 in the bevacizumab group (8%).
In both groups patients receiving or not betablockers were similar for all main clinical characteristics. In the chemotherapy alone group, patients receiving betablockers showed an improved RR (60% vs 33%, p = 0.044) and overall survival (mOS 41.3 vs 25.7 months, p = 0.03, HR: 2.26, 95% CI 1.05-3.24). Only a trend for improved progression-free survival was noticed. In the 115 pa- tients receiving chemotherapy with bevacizumab a trend towards a worse overall survival was seen for patients receiving betablockers, although this was not statistically significant (mOS 16 vs 23.7 months, p = 0.26, HR: 0.64, 95% CI 0.22-1.49). No significant differences were seen in regards of progression-free survival or different response rate patterns between the two groups.
conclusions. Our analysis confirms a potential prognostic role for the use of betablockers in colorectal cancer patients treat- ed with chemotherapy. Our findings are in line with preclinical studies suggesting that beta-adrenergic signalling may regulate cancerogenesis and tumor invasiveness. Our analysis suggests a potential worse outcome for patients on betablockers receiving bevacizumab-based treatment, although the small number of pa- tients precludes any definitive conclusion. We suggest that in fu- ture prospective trials the incidental use of betablockers will be considered a stratification factor for clinical outcome.
A7 myc AmplificAtion impAirs sensitivity to Anti-egfr monoclonAl Antibodies in krAs wild-type metAstAtic colorectAl cAncer (mcrc) pAtients
D’Incecco A.1, Landi L.1, Fountzilas G.2, Kalogeras K.T.2, Geva R.3, Frattini M.4, Rossi E.1, Minuti G.1, Salvini J.1, Ludovini V.5, Crinò L.5, Kako S.6, Robb C.6, Varella-Garcia M.6, Cappuzzo F.1
XV NATIONAL CONGRESS MEDICAL ONCOLOGy SESSION A S7
1Istituto Toscano Tumori, Oncologia Medica, Ospedale Civile, Livorno; 2Hellenic Cooperative Oncology Group (HeCOG), Athens, and Aristotle University of Thessaloniki School of Medi- cine, Thessaloniki, Greece; 3Division of Oncology, Oncology Specialist, gastrointestinal malignancies, Tel-Aviv Sourasky Med- ical Center, Tel-Aviv, Israel; 4Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona, Switzerland;
5S.C. Oncologia Medica, Ospedale S. Maria della Misericordia, Perugia; 6Laboratory of Molecular Pathology, University of Col- orado Cancer Center, Aurora, Colorado, USA
background. Monoclonal antibodies against Epidermal Growth Factor Receptor (EGFR) demonstrated efficacy in metastatic colorectal cancer (mCRC) patients without mutations in the KRAS gene. Previous data in breast and lung cancer sug- gested that MYC gene copy number (GCN) affects sensitivity to anti-EGFR agents. Aim of the present study was to investigate whether MYC GCN influences sensitivity to anti-EGFR strategies in KRAS wild-type (wt) patients who have no benefit from cetux- imab or panitumumab therapy.
material and methods. This retrospective study was con- ducted in a cohort of 206 KRAS wt mCRC patients treated with cetuximab/panitumumab, either alone (N = 19) or in combination with chemotherapy (N = 187). MYC amplification was assessed by fluorescence in situ hybridization (FISH) in primary colorec- tal cancer tissue samples.
results. In the study population response rate (RR) was 32.6%, median progression-free survival (PFS) 5.9 months and median overall survival (OS) 12.6 months. MYC was successful- ly evaluated in 202 cases and resulted amplified (MYC+) in 13 patients (6.3%). Among the 11 patients evaluable for response, MYC+ patients showed a significantly higher progression rate (63.6% versus 27.2%, p = 0.016), shorter PFS (3.0 months versus 6.2 months, p = 0.168) and significantly shorter OS (11.3 months versus 13.0 months, p = 0.038) than individuals lacking MYC amplification (MYC-).
conclusions. Our results suggest MYC amplification as a bio- marker potentially useful for refining selection of KRAS wt mCRC candidate for anti-EGFR treatment.
A8 coi-b (cApecitAbine, oxAliplAtin,
irinotecAn And bevAcizumAb, As first-line treAtment for metAstAtic colorectAl cAncer. A phAse ii itmo study
Di Bartolomeo M.1, Gevorgyan A.1, Ciarlo A.2, Bertolini A.3, Barni S.4, Verusio C.5, Aitini E.6, de Braud F.1, Dotti K.F.1, Pietrantonio F.1, Biondani P.1, Maggi C.1, Bajetta E.7
1Fondazione IRCCS Istituto Nazionale Tumori, Milano; 2Diparti- mento oncologico AUSL 4, Prato; 3Azienda Ospedaliera Valtelli- na e Valchiavenna, Presidio di Sondrio, Sondrio; 4Azienda Ospe- daliera Treviglio, Treviglio; 5Ospedale di Circolo di Busto Arsi- zio, Saronno; 6Dipartimento Interaziendale Provinciale di Onco- logia (DIPO), Mantova; 7Istituto di Oncologia-Policlinico di Monza, Monza
background. A dose-finding phase I/II trial that evaluated the maximum tolerated doses of a combination of three drugs with irinotecan, oxaliplatin and capecitabine (COI regimen) has been conducted (Bajetta, Ann Oncol 2007). We therefore assessed the safety and activity of the combination of COI regimen plus beva- cizumab in patients with colorectal cancer.
material and methods. Patients with colorectal cancer, wich was judged to be unresectable for metastatic disease, were treated with the combination of bevacizumab (5 mg/kg on day 1) and COI regimen (irinotecan 180 mg/m2on day 1, oxaliplatin 85 mg/m2on day 1, capecitabine 2000 mg d2-6; q14), as first-line treatment in six centres in Italy. Induction treatment (COI and be- vacizumab) was administered for a maximum of 8 cycles, fol- lowed by maintenance treatment with bevacizumab (7.5 mg/kg iv on d1, q21) until progression.
results. From June 2009 to March 2011, 51 patients were en- rolled; all patients were assessed for safety and efficacy. Median age was 56 yrs (41-69); M/F: 59%-41%; ECOG PS 0-1/2:90- 6%/4%; metastatic sites: 1/>1: 22%-78%; only liver metastasis 9%; primary tumor on site: 51%, peritoneal carcinosis: 14%;
LDH(>UNL):46%. ORR: 58% (CR: 4%); SD: 37%; PD: 5%;
median PFS: 10 mos (95% CI: 7.3-11.6). Median OS: 22 mos.
The most common adverse event (G1-4) was diarrhoea (86%), vomiting (33%), neutropenia (21%) and peripheral neuropathy (14%). Main adverse events (G3-4): diarrhoea (31%), hyperten- sion (10%), neutropenia (6%), gastrointestinal perforation (2%).
No treatment-related deaths occurred.
conclusions. Results confirm the feasibility of the COI regi- men when combined with bevacizumab. The activity of the regi- men is documented and it appears interesting if we consider the clinical poor prognostic factors of the study population. An analysis on biological parameters is ongoing and it will be avail- able.
Acknowledgements. The authors thank the Italian Trials in Med- ical Oncology (I.T.M.O.) group and Roche S.p.A. for their pro- vided support.
A9 prognostic role of krAs in crc pAtients treAted with bevAcizumAb: A metA-AnAlysis of 12 triAls
Petrelli F., Coinu A., Borgonovo K., Ghilardi M., Cabiddu M., Cremonesi M., Barni S.
Oncologia Medica, Azienda Ospedaliera Treviglio, Treviglio background. The predictive significance of KRAS in ad- vanced colorectal cancer (CRC) treated with anti-epidermal growth factor receptors (EGFR) monoclonal antibodies is well known. However the prognostic and predictive value of KRAS in patients treated with bevacizumab (B) + chemotherapy is not clear. We conducted a systematic review and meta-analysis of published trials, reporting response and survival with first-line, B-based chemotherapy in both wild type (wt) and mutated (mut) metastatic CRC, with the aim to evaluate its predictive and prog- nostic significance.
material and methods. A literature search of PubMed, EM- BASE, Web of Science, and Cochrane Register of Controlled Tri- als was performed. The primary endpoints included objective re- sponse rate (RR), progression-free survival (PFS), and overall survival (OS). The pooled odds ratios (ORs) and hazard ratios (HRs) were extracted or calculated from published data either us- ing fixed effect model or random effect model according to het- erogeneity between studies.
results. Twelve studies were retrieved (6 phase III trials, 1 randomized phase II and 3 single arm phase II studies and 2 prospective series). A total of 2266 patients were analysed (54%
