Tumori Journal Abstract Book - October 2020 - 197

T - Miscellanea
Background: Women continue to be underrepresented in
clinical trials, in spite of WHO recommendation.
A poor representativeness of women in clinical trials does
not allow to measure differences between men and women
in the mechanism of action, metabolism, drug efficacy and
potential adverse events of anticancer treatments. Women
experience higher rates of adverse drug reactions than do
men, due, at least in part, to the fact that women are generally treated with doses extrapolated from studies conducted
mainly on men.
We conducted a meta-analysis to address differences in the
enrollment in phase I/II clinical trials of gastrointestinal
(GI) cancer.
Material and methods: We reviewed all the studies presented at the ASCO GI Cancers Symposium 2020 (n=
923), and analyzed those of Phase I, I/II and pilot studies.
Percentage of males and females, mono or multicenter
studies, kind of cancer and toxicities divided by gender
were retrieved from the abstract . OR for men and women
were calculated and pooled using random effect models
both for mono and multicenter studies. Sensitivities analyses were also performed.
Results: 38 studies met the desired characteristics and
none of these reported gender-specific toxicities. 22
enrolled more males than females, 6 more females, 3 the
same number of males and females and for 7 there were no
gender data. 23 studies were multicentric and 15 monocentric; 12 treated colorectal cancer, 9 pancreas and biliary
tract cancer, 7 all gastro-intestinal cancer, 5 gastric and
esophageal cancer, 4 liver cancer and 1 neuroendocrine
tumor. On the 1191 patients enrolled, 585 were males and
360 females. In 246 cases sex was not reported. Of the 945
patients, males were 62% and females 38%.
Analysis of all the studies showed a trend towards a greater
enrollment of men, but no significant differences were
observed, with OR = 1.78 (0.86 - 3.64, p=0.122) in favor
of enrolling men. No significant heterogeneity was
observed (I^2=0%). Results did not change significantly
for mono or multicenter studies. Sensitivities analyses
excluding one study at the time and using fixed effects also
did not change the results.
Conclusions: Our data suggest that a possible genderbased bias towards men may exists also in phase I/II studies, as the absence of a formal significance is likely due to
the small size of studies included. All efforts should be
done to minimize it, in order to better assess the efficacy
and the safety profile of novel drugs in both sexes.

T41

197
1
Università Cattolica del Sacro Cuore, Roma; 2Department of Medical,
Surgery and Health Sciences, University of Trieste, Trieste; 3Breast Cancer
Unit and Translational Research Unit, Azienda Socio-Sanitaria Territoriale
Cremona, Cremona

Background: Precision medicine, based on molecular and
genotyping patients' characterization, is focused on the
define specific target treatment for any single solid tumor.
BRAF mutation is an oncogenic driver in different cancer
types as indicated in the Cancer Genoma Atlas (TCGA).
Tumor type agnostic therapy is based on targeting genomic
alteration regardless of tumor origin. Within the MOzART
Program, we reported two cases related to the use of
agnostic target treatment driven by results of NGS using
the OncofocusTm Platform (Cambridge, UK).
Clinical results: Case 1 is a chemotherapy refractory
BRAF V600E mutated Intrahepatic cholangiocarcinoma
(ICC) treated with Vemurafenib and Cobimetinib as third
line therapy. The dual BRAF and MEK inhibition resulted
in a partial response of 14 months. Moreover, there was an
improvement in quality of life (QoL) reducing cancer pain
from severe to moderate. Therefore, our patient had partially suspended opioid therapy. Case 2 is a metastatic
chemotherapy refractory Collecting duct of Bellini
(mCDC) carrying a BRAF G466A mutation. The patient
was treated with Dabrafenib and Trametinib in combination in second line therapy obtaining a stable disease lasting 11 months.
Discussion: Strong evidences on melanoma, colorectal
cancer (CRC), non small cell lung cancer (NSLC) and
anaplastic thyroid cancer with BRAF mutations responsive to selective BRAF/MEK pathway inhibitors is well
known nowadays. VE-BASKET and ROAR basket trial
are exploring the efficacy of Vemurafenib and the combination of Dabrafenib/Trametinib respectively in
BRAF V600 mutation-positive other solid tumors.
Studying the relationship between target therapy and
molecular aberration in tumors, the NGS findings supported our decision to treat, in a clinical trial, BRAF
mutated cancers with a very poor prognosis with BRAF
and MEK inhibitors.
Conclusions: Our results confirm the emerging evidences
of molecular tumor profiling for the successful management of solid tumors. Moreover, they highlight the role of
the BRAF mutation as a targetable driver in cancers especially in whose with poor prognosis and/or no available
systematic therapies with a clear clinical benefit.

T42

PROMISING THERAPIES FOR BRAF
MUTATED SOLID TUMORS

Medical records and source
documents for clinical trials in
Italy

Sirico M.1, Bernocchi O.2, Corona S.P.2, Strina C.3, Milani M.3,
Cervoni V.3, Generali D.2

Stabile S.1, Taverniti C.2, Testoni S.3, Federici I.4, Guarrera A.5, Monti
M.3, Cagnazzo C.6

Tumori Journal Abstract Book - October 2020

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