Palbociclib improves survival in Asian postmenopausal women with ER+/HER2- metastatic breast cancer
Palbociclib, in combination with letrozole, significantly improves progression-free survival (PFS) in Asian postmenopausal women with oestrogen receptor-positive, human epidermal receptor 2-negative (ER+/HER2-) metastatic breast cancer compared with letrozole alone, according to a sub-analysis of Asian patients enrolled in the PALOMA-2* study presented at the recent European Society for Medical Oncology Asia 2016 Congress (ESMO Asia 2016) in Singapore.
Median PFS was significantly extended by 11.8 months for Asian patients treated with palbociclib in addition to letrozole compared with those receiving placebo plus letrozole (median PFS, 25.7 vs 13.9 months, hazard ratio [HR], 0.48; 1-sided p=0.0066). The improvement observed in Asians was also similar to that in non-Asian patients (median PFS, 24.8 vs 15.9 months, HR, 0.58; 1-sided p<0.0001). [ESMO Asia 2016, abstract 116O]
The phase III double-blind PALOMA-2 study sub-analysis included 95 Asian patients (median age 60 years) who were randomized to receive either oral palbociclib 125 mg QD at a 3/1 schedule (n=65) or a matching placebo (n=30), in addition to oral letrozole 2.5 mg QD.
“Asian patients mean body weight was 57 kg vs 73 kg in non-Asian patients, which is a 16 kg difference,” observed Professor Im Seock-Ah of Seoul National University in Seoul, South Korea, who also noted that palbociclib dose reduction was performed in more Asian than non-Asian patients (57 percent vs 32 percent) in the palbociclib-letrozole arm, which led to a lower median average daily dose of palbociclib in Asians vs non-Asians (112.5 vs 125 mg). “There is no evidence that dose reduction negatively impacts PFS.”
“[This] begs the question as to whether the 125 mg dose is too high for the vast majority of patients whose weight on average was 16 kg less,” said discussant Professor Stephen Johnston, a Professor of Breast Cancer Medicine of The Royal Marsden NHS Foundation Trust in London, UK.
“Biological drugs ... probably do have dose-related toxicity that is myelosuppressive, and yet they have not been developed as a dose-driven drug to the patient body weight or mass [just like any other drugs],” said Johnston. “I think that might be a lesson for us here from the data we have seen from this abstract.”
Neutropenia was the most common toxicity in both Asian and non-Asian patients in the palbociclib-letrozole arm, with neutropenia of any grade occurring in 95 percent vs 13 percent of Asians in palbociclib vs placebo arms and 77 percent vs 5 percent of non-Asians. Grade 3/4 neutropenia occurred in 63 percent of non-Asians compared with 89 percent of Asians, although none of the Asian cases had neutropenic fever.
“[Neutropenia] was manageable with supportive care and dose modifications, and rarely required permanent treatment discontinuation,” said Im.
Noting that febrile neutropenia occurred in 8 non-Asian patients (1.8 percent) in the palbociclib-letrozole arm, Johnston said “while the incidence of febrile [neutropenia] is very low ... it is still quite a high rate -that means you are having to be monitoring those blood tests at 2 and 4 weeks through the first two cycles to find the right dose for the patient.”
Other nonhaematological AEs of any grade which were more common among Asians in the palbociclib-letrozole than in the placebo-letrozole arms include stomatitis (49 percent vs 20 percent) and nasopharyngitis (26 percent vs 13 percent).
“The safety profile of palbociclib plus letrozole in Asian patients was generally consistent with that observed in non-Asian patients,” said Im. “These data indicate that palbociclib is an acceptable treatment option in Asian patients with ER+/HER2- advanced breast cancer.”
“[Compared with 125 mg, 100 mg] might be a better dose to start patients off in this part of the world,” said Johnston, who recommended future studies be conducted to confirm this.