Journal of Oncology Pharmacy Practice - January 2022 - 179

Liu et al.
179
Patients in this cohort had similar baseline demographics as
the previously treated cohort. The ORR was 85% (95% CI,
70-94). At a median follow-up of 9.2 months, median PFS
was not yet reached.20
Of the thyroid cohort, RET M918T and RET extracellular
cysteine are the most common mutations, consisting of
about 73% of all MTC patients in total. Fifty-five previously
cabozantinib and vandetanib-treated MTC patients
with a median age of 57 years (range: 17-84) were
included. Almost half of the patients (44%) were treated
with both cabozantinib and vandetanib, and 31% received
therapy other than multitargeted kinase inhibitors. The
ORR was 69% (95% CI, 55-81) with five (9%) complete
responses. The median PFS was not reached (95% CI,
24.4-NE). At one year, 86% of the patients continued to
respond to treatment (95% CI, 67-95), and 82% (95% CI,
69-90) remained progression-free. In the cabozantinib
and vandetanib-naïve MTC group, 88 patients with a
median age of 58 years (range: 15-82) were included.
73% (95% CI, 62-82) had an objective response and ten
(11%) of those were complete responses. The median
PFS was 23.6 (95% CI NE-NE).21
Nineteen patients with previously treated RET fusionpositive
thyroid cancer were also included, 13 of which
were papillary subtypes. These patients were heavily pretreated
with four median numbers of previous systemic
regimens. In all, 84% had received radioiodine and 68%
had received sorafenib, lenvatinib, or both. Most patients
were identified with CCDC6 (47%) or NCOA4 (32%)
RET fusion. Overall, 79% (95% CI, 54-94) of them had
an objective response, with one complete responder. At
the median follow-up of 13.7 months, the median PFS
was 20.1 months (9.4-NE). At one year, 71% of responses
(95% CI, 39-88) were ongoing, and 64% (95% CI, 37-82)
of the patients remained progression-free.21
Safety
Patients in the RET-mutantMTCcohort and the RET fusionpositive
NSCLC cohort experienced similar adverse effects.
Some common adverse effects of all grades were increased
aspartate aminotransferase level (AST) (22-51%), increased
alanine aminotransferase level (ALT) (20-45%), and
increased glucose levels (44%). In both cohorts, the four
most common grade 3−4 adverse events were hypertension
(9-18%), increased ALT (9-11%), increased AST (6-8%),
and hyponatremia (7%) in order of decreasing percentages
(Table 3).16,20,21 Patients from both cohorts experienced
grade 5 adverse effects. In the NSCLC group, there were
patients who experienced sepsis, cardiac arrest, multiple
organ dysfunction syndrome, and respiratory failure.20 In
the thyroid cancer group, there were patients who experienced
hemoptysis, postprocedural hemorrhage, sepsis,
cardiac arrest, and cardiac failure.21 The grade 5 adverse
events in both groups were assessed by the investigators
who concluded that these events were not related to selpercatinib.
Among the patients who received selpercatinib,
30% required dose reductions and 2% required discontinuation
of therapy due to adverse effects.16,20,21
Drug interactions
Selpercatinib is metabolized predominantly by CYP3A4.
Concomitant administration of strong CYP3A4 inhibitors
or inducers should be avoided.16
Additionally, acid-reducing agents decrease selpercatinib
plasma concentrations. In clinical studies, proton-pump
inhibitor (PPI) decreased selpercatinib area under the curve
(AUC) by 69% and maximum concentration (Cmax) by 88%
when selpercatinib was administered on an empty
stomach.16 However, PPI did not significantly change the
AUC and Cmax when selpercatinib was administered with
food. Avoid concomitant use of PPIs, H2 receptor antagonists,
and locally acting antacids with selpercatinib.
However, if acid suppressive therapy is necessary, advise
patients to take selpercatinib with food. If coadministration
with a H2 receptor antagonist or an antacid cannot be
avoided, modify the administration time. No clinically significant
differences in selpercatinib pharmacokinetics were
observed when H2 receptor antagonist was given 10 h prior
to and 2 h after the selpercatinib dose. Antacid can be taken
2 h before or 2 h after selpercatinib.16
Selpercatinib is associated with concentrationdependent
QTc interval prolongation. In a QT study
involving healthy subjects, the largest mean increase in
QTc is predicted to be 10.6 ms (upper 90% CI:
12.1 ms).16 In clinical trials, 6% of patients had an
increase in QTcF interval to >500 ms and 15% of patients
had an increase in the QTcF interval of at least 60 ms
over baseline.16,20,21 Prior to initiating selpercatinib and
during treatment, assess QT interval, electrolytes, and
thyroid-stimulating hormone (TSH) and correct hypokalemia,
hypomagnesemia and hypocalcemia. Monitor QT
intervals more frequently in patients who require treatment
with medications known to prolong the QT interval
or strong and moderate CYP3A inhibitors.16
Pralsetinib
Efficacy
Pralsetinib was first approved for metastatic RET fusionpositive
NSCLC based on the data from the phase I/II
ARROW clinical trial in September 2020.19 Eighty-seven
patients with metastatic RET fusion-positive NSCLC previously
treated with platinum chemotherapy were evaluated.
Majority of the patients received pralsetinib at the
recommended phase 2 dose of 400 mg orally once daily
in phase 2. The median age was 60 years (range, 28-85).
Patients received a median of two prior systemic therapies
Journal of Oncology Pharmacy Practice - January 2022

Table of Contents for the Digital Edition of Journal of Oncology Pharmacy Practice - January 2022
