Adding Lynparza to Presurgical Chemo May Not Boost TNBC Outcomes


The addition of Lynparza to presurgical chemotherapy did not improve outcomes for patients with basal-like BRCA wild-type triple-negative breast cancer.

Adding Lynparza (olaparib) to carboplatin and paclitaxel did not improve outcomes in the presurgical treatment setting for patients with basal-like BRCA wild-type triple-negative breast cancer (TNBC).

Study findings — which were presented at the 2024 AACR Annual Meeting — compared pathologic complete response (pCR; lack of cancer found in tissue biopsies), event-free survival (EFS; time without complications from cancer) and overall survival (OS; time from treatment until death from any cause) among treatment groups.

The PARTNER trial showed no significant differences in pCR rates for patients treated with Lynparza compared with chemotherapy alone. Rates at surgery were 51.1% vs 52.4%, respectively. The 36-month EFS rates were 80% vs 79% and the 36-month OS rates were 90% vs 87%, respectively.

Study highlights:

  • Adding Lynparza to certain presurgical chemotherapy drugs did not make a difference in how well treatment worked for certain patients with triple-negative breast cancer, according to a study.
  • The study looked at how well patients responded to treatment, how long they went without complications from cancer and how long they lived after treatment.
  • The study showed that the combination of Lynparza with chemotherapy did not improve outcomes compared to chemotherapy alone, and it caused more side effects for some patients.
  • The next steps include further research to understand why some patients respond differently to treatment and exploring new treatments, like immunotherapy, for TNBC.

“[When] looking at the survival endpoints by pCR in this triple-negative wild type cohort, pCR shows a strong association with long-term outcomes,” Dr. Karen Pinilla Alba, a medical oncologist and a clinical researcher in the Department of Oncology at the University of Cambridge Cancer Research, UK Cancer Centre, said in a presentation of the data. “Patients with a pCR achieved a 36-month PFS of 90% versus a 36-month PFS of 70% in those who did not achieve pCR. This difference was statistically significant. Similarly, researchers observed more deaths in the non-PCR group with a 36-month OS of 83% for those who did not achieve a pCR. This compared with 96% for patients who achieved pCR.”

Alba said the lack of improvement in pCR, EFS and OS were “in sharp contrast to the BRCA-mutated cohort.” However, “the gap schedule regimen provides a biologically relevant concept that should be considered when testing future PARP inhibitor combinations.”

Additionally, the pCR rates were 65% in tumor-infiltrating lymphocytes (TILs) of at least 60% group versus 47.9% in the TILs less than 60% group.

Previous research showed that higher levels of TILs was associated with improved survival in TNBC.

The PARTNER Trial for TNBC

The trial enrolled patients with TNBC with ER-negative, HER2-negative or germline BRCA wild-type disease with any hormone status. Stage 1 evaluated safety in 75 patients. Stage 2 was the preplanned selection of the research arm examining safety, efficacy and compliance/convenience in 159 patients. Stages 1 and 2 randomly assigned patients to one of three groups: the control arm of carboplatin and paclitaxel; the combination gap-schedule arm of carboplatin and paclitaxel plus Lynparza on days 1 to 14; or the combination non-gap schedule arm of carboplatin and paclitaxel plus Lynparza on days 2 to 10. Anthracycline-based chemotherapy and surgery followed.

The combination non-gap schedule arm was stopped after the first two stages. Patients received the chemotherapy combination with or without Lynparza on days 3 to 14 followed by anthracycline-based chemotherapy and surgery. Patients enrolled also had TILs. Further, the primary endpoint of the study was pCR. Secondary endpoints included EFS and OS.

“PARTNER is the first clinical trial to test the combination of [Lynparza] in combination with platinum-containing chemotherapy in the [presurgical] setting of selected with basal-like BRCA wild-type TNBC,” Alba noted.

Additional Data, Safety and Next Steps

“Subgroup analysis didn’t show any differences among age, tumor size, [and] histopathological involvement of lymph nodes and TILs. pCR by TILs was consistent with what has been reported previously,” Alba said. “[There were] no significant differences in pCR rates in each TILs group between the research and control [arms].”

Further, grade 3 or higher side effects occurred in 64.2% of patients in the Lynparza arm compared with 58.7% in the chemotherapy-alone arm. Serious side effects occurred at rates of 34.0% versus 34.6%. They were attributed to carboplatin (21.3% versus 18.2%), paclitaxel (22.3% vs 17.5%) and Lynparza(16.0% versus not applicable). In the Lynparza arm, 7.4% of patients discontinued treatment due to toxicity versus 8.2% in the chemotherapy arm. Additionally, red blood cell transfusion was required in 51.4% versus 30.5% of patients during chemotherapy, respectively.

“What are the next steps?” Dr. Hope S. Rugo, of the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, asked in a discussion of the data. “For TNBC, it’s critical that we have further characterization of a potential set of biomarkers to determine response in this larger population where we run out of treatment options and face difficulties. Also, combinations with immunotherapy, potentially in the post-neoadjuvant setting, are quite intriguing.”

Alba added that TNBC heterogeneity is going to be further investigated by the PARTNER Trial Consortium.
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