Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affectclinical outcome of metastatic breast cancer patients
Abstract
Data di Pubblicazione:
2021
Citazione:
Drug-drug interactions between
palbociclib and proton pump
inhibitors may significantly
affectclinical outcome of
metastatic breast cancer
patients / Del Re, M.; Omarini, C.; Diodati, L.; Palleschi, M.; Meattini, I.; Crucitta, S.; Isca, C.; Fogli, S.; Bleve, S.; Lorenzini, G.; Fontana, A.; Livi, L.; Piacentini, F.; De Giorgi, U.. - In: TUMORI. - ISSN 0300-8916. - 107:(2021). ( Abstract Book of the 23rd National Congress of Italian Association of Medical Oncology (AIOM) Virtual Meeting 22-23-24 October 2021).
Abstract:
Background: Proton pump inhibitors (PPIs) are widely
used in cancer patients to mitigate adversegastroesophageal
events polypharmacy-associated. However, drugdrug
interactions (DDIs) atabsorption level should be
considered as it may affect clinical outcome. Palbociclib is
a weak basewith pH-dependent solubility that rapidly
decreases as pH increases above 4.5 (Clin Pharmacol
DrugDev 2017;6:614-6).
The current study was aimed at investigating the effect of
concomitant PPIs on palbociclibprogression free survival
(PFS) in metastatic breast cancer (mBC) patients.
Materials and methods: ER+, HER-2- mBC patients
candidate to palbociclib as first line treatment were
enrolled in thisretrospective observational study. Patients
were defined as “no concomitant PPIs” if no PPI wereadministered
during palbociclib, and as “concomitant PPIs”
if the administration of PPIs covered theentire or not less
than 2/3 of treatment with palbociclib. All clinical interventions
were madeaccording to clinical practice.
Results: A total of 112 patients were enrolled; 56 belonged
to “no concomitant PPIs” during palbociclibtreatment and
55 to the "concomitant PPIs” group. Seventy-one patients
were endocrine sensitive(ES) and were administered palbociclib
+ letrozole and 43 were endocrine resistant (ER)
and weretreated with palbociclib + fulvestrant. The most
prescribed PPI was lansoprazol. Patients werestratified
according to PFS, showing that patients taking PPIs had a
shorter PFS compared to patientsassuming palbociclib +
hormone-therapy alone (14 vs 38 months, p<0.0001).
Multivariate analysisconfirmed the use of concomitant
PPIs as the only independent predictive factor for shorter
PFS(p=0.0002). PFS was significantly longer in ES mBC
with no concomitant PPIs compared to patientstaking PPIs
or ER patients with and without PPIs (p<0.0001). No correlation
with adverse events wasfound considering G>2
hematological toxicities.
Conclusions: The present study demonstrates that concomitant
use of PPIs in mBC patients treated withpalbociclib
A – Breast Cancer 13
has a detrimental effect on PFS. Therefore, it is recommended
to prescribe PPI withcaution in these patients, or
administering H2-antagonists or PPI for very short periods.
used in cancer patients to mitigate adversegastroesophageal
events polypharmacy-associated. However, drugdrug
interactions (DDIs) atabsorption level should be
considered as it may affect clinical outcome. Palbociclib is
a weak basewith pH-dependent solubility that rapidly
decreases as pH increases above 4.5 (Clin Pharmacol
DrugDev 2017;6:614-6).
The current study was aimed at investigating the effect of
concomitant PPIs on palbociclibprogression free survival
(PFS) in metastatic breast cancer (mBC) patients.
Materials and methods: ER+, HER-2- mBC patients
candidate to palbociclib as first line treatment were
enrolled in thisretrospective observational study. Patients
were defined as “no concomitant PPIs” if no PPI wereadministered
during palbociclib, and as “concomitant PPIs”
if the administration of PPIs covered theentire or not less
than 2/3 of treatment with palbociclib. All clinical interventions
were madeaccording to clinical practice.
Results: A total of 112 patients were enrolled; 56 belonged
to “no concomitant PPIs” during palbociclibtreatment and
55 to the "concomitant PPIs” group. Seventy-one patients
were endocrine sensitive(ES) and were administered palbociclib
+ letrozole and 43 were endocrine resistant (ER)
and weretreated with palbociclib + fulvestrant. The most
prescribed PPI was lansoprazol. Patients werestratified
according to PFS, showing that patients taking PPIs had a
shorter PFS compared to patientsassuming palbociclib +
hormone-therapy alone (14 vs 38 months, p<0.0001).
Multivariate analysisconfirmed the use of concomitant
PPIs as the only independent predictive factor for shorter
PFS(p=0.0002). PFS was significantly longer in ES mBC
with no concomitant PPIs compared to patientstaking PPIs
or ER patients with and without PPIs (p<0.0001). No correlation
with adverse events wasfound considering G>2
hematological toxicities.
Conclusions: The present study demonstrates that concomitant
use of PPIs in mBC patients treated withpalbociclib
A – Breast Cancer 13
has a detrimental effect on PFS. Therefore, it is recommended
to prescribe PPI withcaution in these patients, or
administering H2-antagonists or PPI for very short periods.
Tipologia CRIS:
Abstract in Rivista
Elenco autori:
Del Re, M.; Omarini, C.; Diodati, L.; Palleschi, M.; Meattini, I.; Crucitta, S.; Isca, C.; Fogli, S.; Bleve, S.; Lorenzini, G.; Fontana, A.; Livi, L.; Piacentini, F.; De Giorgi, U.
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