PALOMA-2 study findings suggest that first-line palbociclib does not improve overall survival when added to letrozole for estrogen receptor-positive, HER2-negative advanced breast cancer, but the analysis was hindered by missing data.

The quality of life of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer remains largely unchanged by the addition of palbociclib to first-line fulvestrant, suggest data from the FLIPPER trial.

Palbociclib plus endocrine therapy does not improve progression-free survival compared with capecitabine in women with aromatase inhibitor-resistant metastatic breast cancer, results of the phase 3 PEARL study show.

The PENELOPE-B investigators have found no invasive disease-free survival benefit with a 1-year course of palbociclib alongside endocrine therapy for hormone receptor-positive breast cancer patients who did not achieve a complete pathologic response to neoadjuvant chemotherapy.

Erica Mayer explains why she believes the story of adjuvant palbociclib in hormone receptor-positive, HER2-negative, early-stage breast cancer is not yet over despite the failure of the PALLAS study to meet its primary endpoint.

Adding palbociclib to fulvestrant as first-line therapy improves 1-year progression-free survival in postmenopausal women with hormone receptor-positive, HER2-negative, endocrine-sensitive, metastatic breast cancer, shows the phase 2 FLIPPER trial.

The addition of palbociclib to adjuvant endocrine therapy does not prolong invasive disease-free survival in hormone receptor-positive, HER2-negative, stage II–III breast cancer, shows the phase 3 PALLAS trial.

PALOMA-3 trial findings show that overall survival is significantly improved with the addition of the CDK4/6 inhibitor palbociclib to fulvestrant in patients with hormone receptor-positive, HER2-negative advanced breast cancer and sensitivity to prior endocrine therapy.

Noting that in adjuvant trials of the other CDK4/6 inhibitors abemaciclib and palbociclib, the drugs were administered for up to 2 years, Slamon explained that the 3-year duration was chosen for NATALEE as an extended duration “is crucial to prolong cell cycle arrest and drive more tumor cells into irreversible senescence.”

The discussant said that the PFS HRs for both the DAWNA-1 trial of endocrine-resistant disease and the DAWNA-2 trial of endocrine-sensitive tumors are “consistent” with phase 3 trial findings for palbociclib, ribociclib, and abemaciclib in these settings.

The most common prior CDK4/6 inhibitor was palbociclib (84%) followed by ribociclib (11%), palbociclib plus another CDK4/6 inhibitor (3%), and abemaciclib (2%).

An analysis of the phase 3 PALLAS trial has shown no significant increase in SARS-CoV-2 test positivity and symptomatic infection with the adjuvant use of the CDK4/6 inhibitor palbociclib alongside endocrine therapy in patients with early breast cancer.

Women with hormone receptor-positive, HER2-negative metastatic breast cancer benefit from switching from an aromatase inhibitor to fulvestrant in palbociclib combination therapy when an ESR1 mutation is detected without disease progression, phase 3 PADA-1 trial data show.

Women with hormone receptor-positive, HER2-negative metastatic breast cancer benefit from switching from an aromatase inhibitor to fulvestrant in palbociclib combination therapy when an ESR1 mutation is detected without disease progression, phase 3 PADA-1 trial data show.

The phase 2 trial included patients who had no more than two prior lines of hormone therapy without chemotherapy and had experienced disease recurrence or progression on palbociclib or ribociclib, explained Geoffrey Lindeman (Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia) at the 2021 ASCO Annual Meeting.

All participants had previously received endocrine therapy, 30% had received one line of chemotherapy in the metastatic setting, approximately a fifth had received the CDK4/6 inhibitor palbociclib, and 41% had previously been treated with neoadjuvant or adjuvant taxane therapy.

Ruth O'Regan comments on the monarchE trial of abemaciclib and the PENELOPE-B and PALLAS trials of palbociclib investigating CDK4/6 inhibitor therapy in the adjuvant, hormone receptor-positive, early-stage breast cancer setting (6:35).

George Sledge Jr speculates on the reasons for the contrasting results of the monarchE and PALLAS trials of adjuvant abemaciclib and palbociclib, respectively, in hormone receptor-positive, early-stage breast cancer.

The investigators also point out the three CDK4/6 inhibitors had differing AE profiles, such that palbociclib and ribociclib were primarily associated with hematologic toxicity and abemaciclib with diarrhea and fatigue.

Yet, cost-effectiveness analyses with palbociclib in Canada , the USA , and Switzerland concluded that it is very unlikely that palbociclib in the first line is cost-effective at current pricing.