A neoadjuvant regimen without chemotherapy led to similar results for breast cancer, while allowing a majority of patients with early stage disease at high risk to avoid adjuvant cytotoxic therapy, according to updated results from ‘a randomized trial.
The 40-month progression-free survival (PFS) was 87% for patients who received chemotherapy or the hormonal agent letrozole plus the CDK4 / 6 inhibitor palbociclib (Ibrance). Of 11 disease progression events, three occurred in the non-chemotherapy arm, compared with eight in patients who received neoadjuvant chemotherapy. Invasive disease free survival (iDFS) and breast cancer specific survival (BCSS) also did not differ significantly between treatment groups.
Overall survival favored the chemotherapy control arm, but the majority of deaths in the palbociclib-letrozole arm were unrelated to breast cancer, reported Suzette Delaloge, MD, of the Institut Gustave Roussy in Villejuif, France, to the European Society for Medical Oncology (ESMO) Virtual Breast Cancer Congress.
“In this high-risk population of patients with early luminal A positive and luminal B breast cancer – who had a median MMR [risk of recurrence] score of 70 to 73, the neoadjuvant letrozole and palbociclib led to pathological response rates that did not differ significantly from those obtained with chemotherapy, ”she said. survival and invasive disease-free survival were equivalent. “
“Unfortunately, this study was insufficient for definitive conclusions, but it strongly suggests that such a preoperative approach without letrozole-palbociclib chemotherapy merits further exploration and could be an option for a chemotherapy-free regimen in some cases,” Delaloge added. .
As Previously reported, the primary endpoint of the trial was pathologic complete response (pCR), defined as the residual cancer burden (RCB) 0/1. More patients reached the endpoint with initial chemotherapy, but the difference was not statistically significant, said ESMO guest presenter Hope Rugo, MD, of the University of California, San Francisco. However, the level of RCB 3 before surgery did not differ between groups.
“The overall survival of patients who received chemotherapy appears to be better, but the very small numbers make interpretation of this difference impossible, and the lack of difference between event-free survival, iDFS and BCSS is impressive.” , said Rugo. “This is a small study with relatively short follow-up, even for high-risk hormone receptor positive diseases. However, we have recently seen trials with CDK4 / 6 inhibitors that this brief follow-up can be very significant, even in high-risk diseases. “
“The heterogeneity of the use of post-surgical chemotherapy in the endocrine therapy arm is difficult to interpret,” she continued. “Considering this and the small numbers, there appears to be little impact on short-term outcomes. Short-term laboratory parameters are clearly more informative after and during neoadjuvant endocrine therapy than pCR. The trial, as well as data from previous studies, indicate that this is the case. The antiproliferative response is enhanced with CDK4 / 6 inhibitors, but it is interesting to note that this does not translate into a difference in pCR. lack of impact on longer-term results to date provides support for ongoing trials. “
Delaloge reported secondary results of NeoPAL trial who compared the chemotherapy-free regimen to standard preoperative chemotherapy in 106 patients with high-risk luminal breast cancer. After surgery, patients in both arms received adjuvant endocrine therapy. Patients who did not achieve RCB 0/1 status on the letrozole-palbociclib neoadjuvant regimen were offered chemotherapy in addition to adjuvant endocrine therapy. Subsequently, 23 of the 53 patients in the experimental arm received adjuvant chemotherapy.
The 0/1 BCR rates were 7.6% with the chemotherapy-free regimen and 15.7% with the neoadjuvant chemotherapy. The clinical response rates were 55.5% with letrozole-palbociclib and 53.3% with chemotherapy. Two patients had complete responses, both in the chemo-free arm. The breast-conserving surgery rate was 69% in each arm.
PFS was virtually identical in both arms at 40 months (HR 1.01, 95% CI 0.36-2.90, P= 0.98). The iDFS analysis favored the letrozole-palbociclib arm but did not reach statistical significance (HR 0.83, 95% CI 0.31-2.23, P= 0.71). Analysis of PFS by RCC score showed no difference between patients who achieved a 0/1 RCB or 2/3 RCB in either treatment arm. A total of 13 iDFS events occurred: 11 cases of disease progression (eight in the control arm) and two second cancers (both in the experimental arm).
Seven patients died during the study, all except one in the experimental arm, resulting in an advantage for the control group (P= 0.047). Of the six deaths in the letrozole-palbociclib arm, two were due to breast cancer, two to intercurrent disease, one to suicide, and one to alcoholic cirrhosis. Breast cancer was the only death in the chemotherapy arm.
No unexpected safety issues arose during the study, but the arm without chemotherapy had a more favorable profile.
NeoPAL was supported by Pfizer and NanoString.
Delaloge revealed relevant relationships with Pfizer, AstraZeneca, Roche, Merck, Sanofi, Lilly Novartis, Bristol Myers Squibb, Orion, Daiichi, Puma and Pierre Fabre.
Rugo revealed relevant relationships with Pfizer, Merck, Novartis, Lilly, Genentech, Odonate, Daiichi, Seattle Genetics, Eisai, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, AstraZeneca, Immunomedics, Puma, Samsung and Mylan.