Tumori Journal Abstract Book - October 2020 - 40

40	
used to identify, among differentially methylated genes, a
prognostic signature of functionally methylated genes.
Results: Noteworthy, twelve functionally methylated genes
yielded a hierarchical clustering of patients in two welldefined clusters with hypermethylated tumors characterized
by a significantly worse relapse-free and overall survival
compared to hypomethylated cancers. Interestingly, the
poor prognosis cluster was enriched of CIMP-high and
MSI-like cases. Furthermore, methylation events were
enriched in genes located on q-arm of chromosomes 13 and
20, two chromosomal regions with gain/loss alterations
strongly associated with adenoma-to-carcinoma progression. Finally, the expression of the 12-genes signature and
MSI-enriching genes was confirmed in two independent
oxaliplatin- and irinotecan-resistant CRC cell lines.
Conclusions: These data represent the proof of concept
that the hypermethylation of specific sets of genes may
provide prognostic information being able to identify a
subgroup of mCRCs with poor prognosis.

B20
Efficacy and safety of
regorafenib (REG)-to-trifluridine/
tipiracil (FTD/TPI) sequencing
and vice versa in refractory
metastatic colorectal cancer
(mCRC): a multicenter real-life
experience
Signorelli C.1, Chilelli M.G.1, Morandi M.G.2, Grande R.3, Spinelli
G.P.4, De Marco S.5, Sperduti I.6, Ceribelli A.2, Ruggeri E.M.1
1
Medical Oncology Unit, Belcolle Hospital, Viterbo; 2Medical Oncology Unit,
San Camillo de Lellis Hospital, Rieti; 3Medical Oncology Unit, ASL Frosinone,
Frosinone; 4UOC Oncology, University of Rome "La Sapienza", ASL Latina,
Aprilia (LT); 5Medical Oncology Unit, San Camillo Forlanini Hospital, Roma;
6
Biostatistics Unit, IRCCS Regina Elena National Cancer Institute, Roma

Background: REG and FTD/TPI have demonstrated significant improvements in overall survival (OS) in patients
(pts) with refractory mCRC. The aim of our study was to
evaluate the efficacy and safety profiles of both agents
administered in sequence in the real world practice.
Materials and methods: Clinical data of pts treated
beyond the 2°line with REG or FTD/TPI between October
2015 and May 2020, were retrospectively collected in 5
institutes in the Lazio Region.
Results: Overall, we included 62 pts but we focused our
attention on the 2 groups of pts treated with sequencing: 13
pts (21%) with FTD/TPI-to-REG and 11 pts (17.7%) with
REG-to-FTD/TPI. M/F=15/9; median age was 70 years
(ys) (45-80); median duration of follow-up was 10 months
(ms) (4-50); median duration of sequence treatment was
9.5 ms (5-17); median number of cycles was 8.5 (4-25). A
median of 9.6 cycles per pt were administered. Performance
Status ECOG ranged between 0 (29.1%) and 2 (8.3%). 13

Tumori Journal 106(2S)
pts (54.1%) received active 3 lines of treatment, 10 pts
(41.6%) 2 lines and 1 pt (4.1%) 4 lines before the sequences
above. 11 pts (45.8%) experienced g3-4 toxicities (36.3%
in FTD/TPI-to-REG vs 63.6% in REG-to-FTD/TPI).
Toxicities, such as neutropenia (g4 23.07%), anemia (g3
7.6%) and leucopenia (g3 7.6%) occurred more with FTD/
TPI-to-REG, while events such as hand-foot skin reaction
(g3 36.3%) and fatigue (g3 9.09%) were reported with
REG-to-FTD/TPI. No therapy related death was reported.
Median OS for all patients was 16.7 ms (95% CI=7,625,7) regardless of therapy administered; in particular,
20.8 ms in REG-to-FTD/TPI sequence (95% CI=1,8-39,8,
p=0.62), not estimable in the FTD/TPI-to-REG group.
Best 1-y survival rate was 46.1% with FTD/TPI-to-REG
sequence vs 36.3% of REG-to-FTD/TPI group. No differences were found for median progression free survival: 5
ms with FTD/TPI-to-REG (95% CI=2,7-7,4) vs 4.1 ms
with REG-to-FTD/TPI (95% CI=2,5-5,7) (p=0.78). Partial
response was achieved only in 1 out of 11 pts (9.09%) for
REG-to-FTD/TPI. Disease control was greater with REGto-FTD/TPI (54.5%) vs 23.1% of FTD/TPI-REG.
Conclusions: With the limit of the sample size, we conclude
that in our real-world experience, both sequences REG-toFTD/TPI and vice versa could extend survival while only
REG-to-FTD/TPI stabilizes cancer growth. Prevalent toxicities seem dependent from the first drug of the sequencing.
So it could be important to decide which agent in the
sequence should be administered in the beginning.

B21
Drug-drug interactions and
Pharmacogenomic evaluations
in Colorectal Cancer Patient:
the new Drug-PIN® system
comprehensive approach
Roberto M.1, Rossi A.2, Panebianco M.2, Pomes L.M.3, Simmaco M.4,
Mazzuca F.5, Marchetti P.5
1
Dipartimento di Medicina Clinica e Molecolare, Università "La Sapienza",
AOU Sant'Andrea, Roma; 2UOC Oncologia Medica, AOU Sant'Andrea,
Roma; 3Department of Neuroscience, Mental Health, and Sensory Organs
(NESMOS), Sapienza University; UOD Diagnostica Molecolare avanzata,
AOU Sant'Andrea, Roma; 4UOD Diagnostica Molecolare avanzata, AOU
Sant'Andrea, Roma; 5Dipartimento di Medicina Clinica e Molecolare, UOC
Oncologia, AOU Sant'Andrea, Roma

Background: Polypharmacotherapy is a relevant issue in
cancer patients, since a Drug-Drug Interaction (DDI) condition may affect both treatment efficacy and toxicity. The
combination of DDIs and individual genetic polymorphisms, called Drug-Drug-Gene Interaction (DDGI), is a
new fascinating concept of personalized medicine. Thus, we
present the use of Drug-PIN® (Personalized Interactions
Network) software in Patients treated for colorectal cancer
(CRC) at our institution.
Tumori Journal Abstract Book - October 2020

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