Tumori Journal Abstract Book - October 2020 - 99

E - Breast Cancer	

E03*
Resistance to CDK4/6 inhibitors
(CDK4/6i): the Clinical Usefulness
of Liquid Biopsy in Metastatic
Breast Cancer (MBC)
Raimondi L.1, Gozzi E.2, Bitca V.2, Pietranera M.2, Rossi L.2, Spinelli G.P.2
1

Università La Sapienza, Roma; 2Università La Sapienza, Aprilia

Background: Despite therapeutic improvements, most
patients (pts) acquire resistance to CDK4/6i. KRAS tumor
mutations have been associated with worse PFS in several
tumor types but have not been analysed extensively in breast
cancer in the era of Palbociclib and Fulvestrant (P+F). In
this study, using liquid biopsy, we evaluated the opportunity
to reveal the onset of resistance to P+F, detecting KRASmutated ctDNA and CDK4/9 expression in HR+/HER2MBC treated with P+F as first metastatic line.
Methods: We assessed 106 consecutive pts with HR+/
HER2-MBC treated with P+F as first-line metastatic therapy, with sensitivity to previous endocrine therapy (Dec17Mar20). Using Bio-Rad QX200 ddPCR system and
exoRNeasy kit we determined KRAS ctDNA levels and
CDK4/9 expression in plasma, respectively.
Results: A total of 948 blood samples were collected. In
54%(57 pts)we observed KRAS-mutated ctDNA before
starting P+F: the detection was associated with lower LMr
and significantly correlated with the onset of resistance to
P+F within 6months from the evidence of KRAS mutation
and worse PFS (p<0.001). At 18-month follow up[1-NA],
pts with baseline KRAS-mutated ctDNA, low CDK4 levels
and overexpression of CDK9 had a median PFS of 3
months [1-6months,95%CI 0.8-3.6]contrary to ones with
KRAS wild-type whose PFS has not yet been reached
(p<0.001). Correlating the results of liquid biopsy both to
tumoral burden and pts clinical features, we observed a
higher KRAS-mutated circulating copies-number in those
patients with two or more metastatic sites (p<0.001) and
with lower lymphocyte-monocyte ratio (p=0.003).
Conclusions: Despite the study's limitations,our data suggest the appearance of KRAS mutations leads to P+F resistance acquisition within 6months and provide critical
information for the prediction of therapeutic responses in
MBC. Monitoring KRAS status with liquid biopsy, we could
predict who will take advantage from P+F, decreasing
wastes of resources ensuring the best pts' quality of life.

E04*
Moving from the CLEOPATRA study
to real life: final results from the
G.O.N.O. SUPER trial
Garrone O.1, Giarratano T.2, D'Onofrio L.3, Michelotti A.4, Blondeaux
E.5, Saggia C.6, Merlini L.7, Cazzaniga M.E.8, Donadio M.9, Farnesi

99
A.10, Montemurro F.11, La Verde N.M.12, Coltelli L.13, Vandone A.M.1,
Collovà E.14, Blasi L.15, Ardito R.16, De Conciliis E.17, Airoldi M.9,
Merlano M.C.1
1

Azienda Ospedaliera S. Croce e Carle Ospedale di Insegnamento, Cuneo;
Istituto Oncologico Veneto IRCCS, Padova; 3Campus Biomedico, Roma;
4
Azienda Ospedaliera Universitaria, Pisa; 5IRCCS Ospedale Policlinco San
Martino, Genova; 6Azienda Ospedaliera Universitaria Maggiore della Carità,
Novara; 7Ospedale San Bortolo, Vicenza; 8Ospedale San Gerardo, Monza;
9
Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino;
10
Azienda USL Toscana Nordovest, Livorno; 11Candiolo Cancer Center FPOIRCCS, Candiolo (TO); 12ASST Fatebenefratelli Sacco, Milano; 13Ospedale
Lotti, Pontedera; 14ASST Ovest Milanese, Legnano; 15ARNAS Civico, Palermo;
16
IRCCS CROB, Rionero in Vulture (PZ); 17Ospedale Cardinal Massaia, Asti
2

Background: The association of Trastuzumab (T) and
Pertuzumab (P) plus taxane is the standard first line therapy
for HER2 positive (HER2+) metastatic breast cancer
(MBC) patients (pts). Results from CLEOPATRA have
underlined a significant advantage both in PFS and OS in
pts treated with T+P and docetaxel (D) over T and D. With
the aim to describe the applicability of CLEOPATRA results
in real world pts, we performed a multicenter, retrospectiveprospective, observational study, in HER-2+ MBC pts.
Material and Methods: We analyzed the outcome of all
HER-2+ MBC pts treated with P+T and taxanes as first
line therapy since the availability of P in Italy, at 18 general and university hospitals.
Results: Up to March 2019, 347 pts were recorded. 5 were
excluded due to incomplete data. Overall data on 342 pts
are evaluated. Main pts characteristics were: median (m)
age 55 y (19-80), m ECOG PS 0 (0-2). 170 pts (49.7%) had
metastatic disease at presentation. HR+ 230 pts (67%);
96/172 pts (56%)received neo/adjuvant chemotherapy
(CT) + T and 119/129 HR+ pts (92%) received adjuvant
endocrine therapy. Visceral involvement was present in
216 pts (63%). Most common metastatic sites:bone 185
pts (54%), liver 138 pts (40%), lung 108 pts (38%), soft
tissues 244 pts (71%); 14 pts (4%) had CNS involvement.
205 pts (60%) and 136 pts (40%) received D and paclitaxel
(Pa) respectively. 1 pt received vinorelbine. M number of
CT cycles was 6 for both drugs (D range 1-14; Pa range
1-24). 144 pts (42%) are on maintenance, 177 pts (52%)
received ET concomitantly with P+T maintenance. ORR
is 77% (CR and PR in 79 and 184 pts respectively), PD in
22 pts. With 198 events recorded (58%), M PFS is 26.9
months (95% CI 20 - 33.8). In 96 pts previously exposed
to adjuvant T, with 66 events (68%), m PFS is 20.7 months
(95% CI 15.6 - 25.8). Any grade leucopenia and neutropenia were recorded in 24% and 26% of pts respectively;
febrile neutropenia in 11 pts. 30 pts (8.8%) developed cardiac toxicity leading to discontinuation of P+T maintenance in 14 pts. Any grade non-hematological toxicities:
diarrhea 162 pts (47%), asthenia 212 pts (62%), peripheral
neuropathy 133 pts (39%).
Conclusions: Our results support the activity and safety of
the combination of CT (D or Pa) plus P and T in real world
HER2+ MBC pts. The advantage is also evident in pts
Tumori Journal Abstract Book - October 2020

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