Tumori Journal Abstract Book - October 2020 - 180

180
platinum-sensitive Epithelial Ovarian Cancer (EOC)
patients carry a germline/somatic BRCA1/2 mutation and
PARPis produced a significant improvement in long-term
disease control. Olaparib, Rucaparib and Niraparib represent a choice for these patients. The aim of this study is to
ievaluate the role of these agents in BRCA1/2-mutated
breast cancer and BRCA1/2-mutated EOC, determining the
improvement in Survival (PFS).
Patients and Methods: A systematic literature review of
Pubmed and abstracts from major oncological meetings
was carried out including all published prospective and
randomized controlled trials (RCTs) using pairwise comparisons designed on BRCA-mutated respectively in MBC
and EOC in all lines of treatment. Meta-analyses were
conducted by random effect model. For HER-2 negative
MBC the primary endpoint was PFS. For EOC we updated
a previous meta-analysis published on 2018 which was
empowered by a Bayesian approach.
Results: Regarding MBC, 10 RCTs for a total of 3127
patients were selected and included in the final analysis. We
reported a trend of benefit for PARPis in terms of Overall
Survival (OS) (HR 0.86; IC 0.73-1.01) and a significant PFS
benefit (HR 0.64; IC 0.55-0.75). About EOC, 10 RCTs for a
total of 4342 patients were selected and included in the final
analysis. In terms of PFS, we performed an indirect comparison. On these bases it is possible to infer that the concomitant
and sequential combination of CT with PARPis was the best
therapeutic strategy. Toxicity analysis showed significant
differences among different PARPis, confirming that the
class effect only regarded the efficacy endpoints.
Conclusions: We highlighted a trend of benefit in survival
endpoints in MBC. A longer follow-up and a better selection
of patients are clearly required. Concerning the EOCanalysis section we confirmed the role of PARPis in this
scenario, hypothesizing that the better performance remains
as sequence to chemotherapy. By the Bayesian analysis we
confirmed the "class-effect" of these agents, too.

T09
SINGLE NUCLEOTIDE POLYMORPHISMS
(SNPs) TO PREDICT TAXANES
TOXICITIES AND EFFECTIVENESS IN
CANCER PATIENTS
Demurtas S.1, Cheli S.2, Cona M.S.1, Dalu D.1, Filipazzi V.1, Fasola
C.1, Rota S.1, Ferrario S.1, Montrasio C.2, Gambaro A.1, Tosca N.1, La
Verde N.1, Clementi E.3

Tumori Journal 106(2S)
by SNPs in genes encoding proteins responsible for pharmacokinetic and pharmacodynamic. This prospective,
monocentric, observational study aims to explore the
effect of known SNPs in the main genes involved in taxanes metabolism and transport, on toxicity and efficacy.
Material and methods: Patients (pts) treated with paclitaxel, docetaxel or nab-paclitaxel were enrolled at the
Department of Oncology of Luigi Sacco Hospital in Milan.
For each patient a blood sample was collected for DNA
extraction. DNA were genotyped by RT-PCR to detect
c.1236C>T, c.2677G>T/A, c.3435C>T SNPs in ABCB1
and CYP3A4*22, CYP3A5*3, CYP2C8*3, CYP2C8*4
SNPs in corresponding genes. AEs were evaluated according to CTCAE v5.0 and efficacy according to RECIST.
Results: 125 pts were enrolled. Grade 2-4 AEs: 47.2%
hematological, 24% neurological, 24.2% gastrointestinal,
10% mucositis, 7.5% nail changes, 3.3% skin reactions,
3.3% hepatic, 10.5% infusion related reaction.
For CYP SNPs: 12% of pts were heterozygous (het) for
CYP3A4*22; 8.8% het for CYP3A5*3; 23.2% het and
1.6% homozygous (hom) for CYP2C8*3; 5.6% het for
CYP2C8*4. For the ABCB1 SNPs, c.1236C>T het in
53.6% and hom in 18.4% of pts; c.2677G>T/A het in 56%
and hom in 19.2%. c.3435C>T het in 48.8% and hom in
24%. There was no statistically significant association
between the investigated SNPs and AEs.
The het genotype of CYP3A4*22 showed an association
with skin reactions in pts treated with paclitaxel and nabpaclitaxel, although without statistical significance
(RR=6.92;95%CI0.47,99.8; p=0.076). CYP2C8*3/*4 variant carriers showed an association, though not statistically
significant, with overall AEs in pts treated with paclitaxel
and nab-paclitaxel (RR=1.28;95%CI0.96,1.67; p=0.089).
There wasn't any statistically significant relationship with
treatment efficacy but there was a trend for ABCB1 3435TT
genotype and a higher treatment response (p=0.153).
Conclusions: The study suggested that CYP3A4*22 and
CYP2C8 SNPs may influence paclitaxel and nab-paclitaxel
toxicity, even if it didn't find any statistically significant association between SNPs and taxanes-induced AEs or efficacy.
The increase of sample size could help to achieve statistical
significance; the population was heterogeneous, but this
reflects clinical practice and the aim of pharmacogenetic
studies is to translate laboratory findings into clinical care.

T10

Department of Oncology, Luigi Sacco Hospital, ASST - Fatebenefratelli - Sacco,
Milano; 2Unit of Clinical Pharmacology Luigi Sacco Hospital, ASST Fatebenefratelli
Sacco, Milano; 3Unit of Clinical Pharmacology, Department of Biomedical and
Clinical Sciences, National Research Council-Institute of Neuroscience, University
Hospital L. Sacco, University of Milano, Milan, Italy, Milano

The impact of drugs modulating
microbiota on the outcome
of advanced cancer patients
treated with immune checkpoint
inhibitors. A new prognostic
"drug score"

Background: Taxanes are used in the treatment of several
solid tumors. Adverse events (AEs) might be influenced

Perrone F.1, Bersanelli M.1, Cortellini A.2, Casartelli C.1, Bordi P.1,
Tiseo M.1, Buti S.1

Tumori Journal Abstract Book - October 2020

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