2024-SABCS-Takeaways - 6

MEDICAL ONCOLOGY CONTINUED
FDA Special Session: New Drug Approvals
T
he latest round
of breast cancer
approvals by
the U.S. Food and Drug
Administration (FDA)
- ribociclib plus an
aromatase inhibitor and
inavolisib plus palbociclib
plus fulvestrant - are
rooted in a framework
developed by Project
Optimus, an agencywide
approach to drug
development that
considers the totality
of orthogonal data
to minimize toxicity,
enhance efficacy,
and improve patient
outcomes. Reviewers
assessed clinical activity,
patient population,
acute and chronic
toxicity and tolerability,
pharmacodynamics,
pharmacokinetics, and
nonclinical data, as well as
MTD. Experts, including
representatives from the
FDA, discussed recent
approvals during a special
session on new drugs at
the 2024 SABCS®.
Ribociclib is a CDK4/6
inhibitor. The FDA first
approved the agent in
2017 in combination with
letrozole for HR-positive,
HER2-negative
metastatic breast cancer
based on data from
the MONALEESA-2
trial. In 2018, data from
MONALEESA-3 and
MONALEESA-7 were
the foundation for an
expanded approval of
ribociclib in combination
with fulvestrant and
aromatase inhibitors.
The latest approval,
based on NATALEE, brings
ribociclib to the adjuvant
setting with nonsteroidal
aromatase inhibitors for
patients with HR-positive,
HER2-negative stage
II and III early breast
cancer who are at high
risk of recurrence.
The manufacturer has
said it is committed to
postmarketing studies
reflecting the racial/
ethnic composition
of the U.S. population
with HR-positive, HER2negative
early-stage
breast cancer, as well as to
an overall survival analysis.
This is not an easy
regimen to tolerate. In
NATALEE, more than half
of the patients who have
received ribociclib (56%)
experienced grade 3-4
toxicities. Neutropenia
and hepatobiliary toxicity
were most common.
Toxicity prompted 23%
of patients to reduce
dose, 66% to interrupt
treatment, and 20% to
discontinue treatment.
Inavolisib is an inhibitor
of PI3K, primarily
PI3Kα. The agent was
approved in combination
with palbociclib and
fulvestrant for endocrineresistant,
PIK3CA-mutant,
HR-positive, HER2negative,
locally
ON THE IMPORTANCE OF QUALITY OF LIFE
" Many patients are going to survive
breast cancer. They need to survive our
treatments as well. "
ANTONIO C. WOLFF, MD, FACP, FASCO, Interim
Director, Johns Hopkins Breast & Gynecologic
Malignancies Group
6
advanced or metastatic
breast cancer following
recurrence on or after
completing adjuvant
ET as detected by an
FDA-approved test.
Between 35% and 40%
of HR-positive breast
cancers have PIK3CA
mutations. Approval was
based on the INAVO120
trial and represents the
first triplet combination
for first-line treatment in
this population.
The most common
toxicities include
neutrophilia,
hyperglycemia, and
thrombocytopenia.
Other common toxicities,
including stomatitis,
diarrhea, and rash, are
known class effects.
Patient-reported
outcomes showed
worsening of diarrhea,
nausea, vomiting,
fatigue, mouth sores,
decreased appetite, rash,
and overall toxicity.
Approval came with
a contemporaneous
approval for the F1LDx
companion diagnostic
to test PIK3CA mutation
status. The test uses nextgeneration
sequencing
to detect substitution,
2024 SABCS®
| Takeaways
https://events.hubilo.com/sabcs2024/session/252169 https://events.hubilo.com/sabcs2024/session/252169
2024-SABCS-Takeaways

Table of Contents for the Digital Edition of 2024-SABCS-Takeaways
