Bologna, 9 Febbraio 2019 AIOM POST ASCO GI REVIEW Updates and News from the GI Cancers Symposium in San Francisco Pancreas Cancer ASCO Poster Review Lisa Salvatore UOC Oncologia Medica Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma
My Personal Selection Neoadjuvant treatment Adjuvant treatment enhancement Elderly pts treatment Elderly Pts Selection and Precision Medicine
My Personal Selection Neoadjuvant treatment Adjuvant treatment enhancement Elderly pts treatment Elderly Pts Selection and Precision Medicine
Why prefer neoadjuvant tx? Higher number of treated pts Better compliance of pts Upfront treatment of micromets Evaluation of tumor chemosensitivity Tumor shrinkage and reduction of N1 and R1 rate Improvement of tissue distribution of CT
Stage I-II PDCA: Surgery vs Neoadjuvant vs Adjuvant Surgery N=1262 Stage I-II PDCA From National Cancer DB Propensity Score Matched Analysis Adjuvant tx N=2660 Neoadjuvant tx N=321 Neoadj + Adj tx N=151 Ivanics et al. ASCO GI 2019 #450
Stage I-II PDCA: Surgery vs Neoadjuvant vs Adjuvant Propensity matched cohort mos (NAT+R/NAT+R+AT): 28.6 mos mos (R/R+AT):22.9 mos p<0.001 Ivanics et al. ASCO GI 2019 #450
Res and BL PDCA: Surgery vs Neoadjuvant CTRT Nagai et al. ASCO GI 2019 #343
Res and BL PDCA: Surgery vs Neoadjuvant CTRT All cases: resected and non resected Resected cases Nagai et al. ASCO GI 2019 #343
Neoadjuvant tx performance Author #abstract Phase Disease Treatment OS mos Ivanics #450 Retrospective Stage I-II Neoadj>Sx>Adj Not specified 36.0 Nagai #343 Retrospective Resectable and border-line Neoadj gem+rt>sx>adj gem+5fu hepatic arterial infusion 37.0 Unno #189 II/III Resectable Neoadj gem+s-1>sx>adj S-1 36.7
Still several open questions Resectable disease: which patients? Resectable vs border-line disease Which chemotherapy regimen? Which is the role of RT? Which RT regimen? Which is the role of postoperative treatment?
SWOG S1505: neoadj mfolfirinox vs Gem+Nab Randomized phase II pick the winner design Primary end-point: 2-yr OS N=147 resectable PDCA Sohal et al. ASCO GI 2019 #414
SWOG S1505: neoadj mfolfirinox vs Gem+Nab 9% Sohal et al. ASCO GI 2019 #414
My Personal Selection Neoadjuvant treatment Adjuvant treatment enhancement Elderly pts treatment Elderly Pts Selection and Precision Medicine
Adj CT with or without RT Shinde et al. ASCO GI 2019 #334
Adj CT with or without RT 3-yr OS RT yes 3-yr OS= 44.6% RT no 3-yr OS= 35.3% p<0.001 HR=0.68 Shinde et al. ASCO GI 2019 #334
Stage I-II PDCA: Adj CT vs CTRT vs CT>CTRT Adjuvant CT N=3031 Resected Stage I-II PDCA From National Cancer DB Adj CTRT N=1307 Adj CT>CTRT N=1329 Jun Ma et al. ASCO GI 2019 #372
Stage I-II PDCA: Adj CT vs CTRT vs CT>CTRT mos C+CRT=23.4 mos mos CRT=20.8 mos p<0.001 mos C+CRT=23.4 mos mos C=20.0 mos p<0.001 Jun Ma et al. ASCO GI 2019 #372
Still several open questions and bias Which RT regimen? All pts benefit from RT? Retrospective analysis Which chemotherapy regimen? NO data with FOLFIRINOX (PRODIGE-24)
My Personal Selection Neoadjuvant treatment Adjuvant treatment enhancement Elderly pts treatment Elderly Pts Selection and Precision Medicine
FOLFIRINOX mpdca pts 75 years Mizrahi et al. ASCO GI 2019 #362 Conroy et al. NEJM 2011
FOLFIRINOX in elderly mpdca pts mos: 11.6 months Conroy et al mos: 11.1 months DCR: 66.7% Conroy et al DCR: 70.2% Mizrahi et al. ASCO GI 2019 #362
My Personal Selection Neoadjuvant treatment Adjuvant treatment enhancement Elderly pts treatment Elderly Pts Selection and Precision Medicine
Dreyer et al. ASCO GI 2019 #285 DNA Damage Response Deficiency
Dreyer et al. ASCO GI 2019 #285 High Replication Stress
Personalized clinical trials via PRECISION-Panc platform Dreyer et al. ASCO GI 2019 #285
DNA Damage Response Deficiency DDR deficiency=12% mpfs=18.5 mos mpdca pts treated with first-line platinum-based CT mpfs=6.9 mos Palacio et al. ASCO GI 2019 #266
PDCA selection Improvement of chemo benefit Significant proportion of clinical actionable alterations Personalized treatment Genetic screening
Take-home messages Neoadjuvant tx can improve outcome of resectable (and border-line) PDCA, but there are still open questions The association of RT with adjuvant CT can improve outcome of resected PDCA, but there are still open questions Combo CT in elderly (and selected) pts can be safe, active and efficacious The enhancement of PDCA pts selection can optimize standard chemo benefit and improve personalized treatment
salvatore.lisa82@gmail.com lisa.salvatore@policlinicogemelli.it