Page 271 - Read Online

Lecchini et al. HCC vascular invasion in sorafenib treatment

Table 3: Dose, duration and response of treatment received other treatments: percutaneous ablative
Characteristics Data treatments (2 patients) or other systemic treatments
Treatment duration (median months) 2.5 such as capecitabine or tivantinib (6 patients).
Response rate
PR 5/84 (6%) Survival analysis based on epidemiological
SD 27/84 (32%)
PD 26/84 (31%) and clinical data and previous treatments
NA 26/84 (31%) Median overall survival was 8.5 months [Figure 1A].
Median daily dose mg (IQR) 800 (600-800) The epidemiological and clinical parameters shown
Patients treated with median dose of 800 mg 53/84 (63%) in Table 1 were assessed as factors that could have
Patients treated with median dose < 800 mg 31/84 (37%) an effect on survival. Only Child-Pugh score (A vs. B;
Dose reduction
Yes 44/84 (52%) P = 0.0289) showed an impact on survival, while the
No 40/84 (48%) remaining epidemiological and clinical characteristics
Adverse events (yes/no) 77 (91.5%)/7 (8.5%) did not show significant differences. History of previous
Asthenia 72/77 (93.5%) treatment for HCC was a positive factor, however
Gastro-intestinal symptoms 63/77 (82%)
Rash, peeling, itchy (general) 48/77 (62%) not achieving statistical significance [Table 4], in
Hypertension 36/77 (47%) particular also considering independently locoregional
HFSR 27/77 (35%) treatments, that represented the most frequent
Alopecia 21/77 (27%)
Bleeding 15/77 (19.5%) treatment, there was no significant impact on survival
Cardiovascular events 0/77 (0%) (not shown). Eight patients with history of different
Reason of treatment suspension tumors showed comparable survival to the remaining
Progressive disease 25/84 (30%) subjects (not shown).
Adverse events 23/84 (27%)
Liver failure 22/84 (26%)
Other reasons 7/84 (9%) Impact on survival of HCC characteristics
PR: partial response; SD: stable disease; PD: progressive disease; Tumor parameters [Table 2] were evaluated as factors
NA: not applied; IQR: interquartile range; HFSR: hand-foot skin potentially influencing survival. Unexpectedly, alpha-
reaction fetoprotein levels, multifocal tumor extended to both
were used to perform the statistical analysis. The lobes as well as extrahepatic spread didn’t influence
survival significantly. Macroscopic vascular invasion
comparison between mean values was performed with was found to be a strong predictor for survival (P =
Student t test for unpaired data. Statistical significance 0.0141) [Figure 1B], while the association of metastasis
was considered for values P < 0.05.
and vascular invasion did not worsen patient outcome.
RESULTS Survival analysis based on response rate,
sorafenib dose and treatment duration
Overall picture All data related to therapy reported in Table 3 were
Results on response rate, treatment duration, sorafenib analyzed as parameters that could influence clinical
dose and side effects are reported in Table 3: PR was outcome. As expected, longer duration of therapy
achieved in 5 patients (6%), SD in 32% and PD in 31% (beyond median time of treatment) was positively
of patients. None of patients achieved a CR. Treatment associated with survival (P < 0.0001) [Figure 1C], even
was discontinued for adverse events or clinical though this may not represent an effect of treatment,
worsening before radiological evaluation in 26 patients since other factors like progressive disease or adverse
(31%). Median treatment duration was 2.5 months. events, could have influenced time on treatment.
Forty patients (48%) received full sorafenib dose Response rate showed a significant impact on survival
(800 mg/day) during all the treatment, while 44 subjects (P = 0.0237) [Figure 1D], with median survival of 12.5
(52%) reduced sorafenib dose. Median daily dose was months in patients with SD or PR compared to 9.5
800 mg. Thirty-seven percent of patients received a months for patients with PD. Dose reduction was a
median dose of 800 mg, while the remaining (63%) a favorable parameter (P = 0.004) as well as drug regimen
minor dose (range 200-600 mg) because of adverse below median daily dose (P = 0.04) [Figure 1E and F].
events. Dose reductions ranged between 5% and
90% of the time on treatment. Most of patients (92.5%) Adverse events and tolerability
developed adverse events: gastro-intestinal symptoms, Sorafenib appeared well-tolerated as in previous
asthenia, rash and skin peeling and high blood studies and registration trials, however adverse events
pressure; the most common adverse event was severe were reported, also in this study. Overall incidence
weight loss associated with asthenia and diarrhea. of adverse effects was 91.5% of this cohort [Table 3].
Finally, 20 patients after sorafenib discontinuation Asthenia, fatigue and gastro-intestinal symptoms

Hepatoma Research ¦ Volume 3 ¦ November 16, 2017 263