Gilead Sciences’ Trodelvy drug extended by 3.2 months the survival of patients with advanced stages of a common type of breast cancer, (i.e. reduced the risk of death by 21%), with the company calling the phase III TROPiCS-02 study results both statistically and clinically significant.
The study, presented at the European Society for Medical Oncology's annual meeting (ESMO) in Paris last week, compares Trodelvy to chemotherapy in 543 patients with hormone-sensitive tumours that test negative for a receptor called HER2 and who had stopped responding to at least two earlier courses of therapy, reports Reuters.
Gilead said interim results from the trial show overall survival for those who received Trodelvy of 14.4 months compared with 11.2 months for chemotherapy patients.
Trodelvy, also known as sacituzumab govitecan, uses a tumour-targeting antibody to deliver an anti-cancer drug.
“The only option for these patients is chemotherapy,” Bill Grossman, head of oncology at Gilead, told Reuters. “I think it's going to be a game changer for these patients going forward.”
The data release comes after Gilead, in March, said the breast cancer study met its main goal of reducing the risk of cancer progression or death, but did not disclose any details.
The company reported some additional details in June, saying the trial met its primary goal by showing progression-free survival – the time until the disease begins to worsen – of 5.5 months for the Trodelvy group versus four months for chemotherapy patients.
It also disclosed that the first analysis showed Trodelvy patients lived a median 13.9 months, compared to 12.3 months for the chemotherapy group, a difference that was not statistically significant.
Gilead said last month it had applied for US approval of Trodelvy for pre-treated hormone receptor positive/HER2 negative metastatic breast cancer. The drug is already approved in the US for previously treated metastatic triple-negative breast cancer and bladder cancer. It is being studied for use in various cancer types.
Earlier this year (June), MedicalBrief reported on the results of the trial for the drug Enhertu, which was shown to enable women with advanced breast cancer to live six months longer than others treated with conventional chemotherapy, according to data from AstraZeneca and the Japanese drug-maker, Daiichi Sankyo.
While these drugs are not without their side-effects and downsides (expense), it was suggested that, after decades of trial and error with antibody-drug conjugates, cancer researchers are finally starting to understand how best to design and use them.
Study details
Sacituzumab govitecan (SG) efficacy in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (MBC) by HER2 immunohistochemistry (IHC) status in the phase III TROPiCS-02 study
P. Schmid, J. Cortés, F. Marmé, H.S. Rugo, S.M. Tolaney, M. Oliveira, D. Loirat, K. Jhaveri, O.K. Yoon, M. Motwani, H. Wang, R.J. Delaney, A. Bardia.0
Presented at ESMO on 10 September 2022
Abstract
Background
Tumours with HER2 IHC1+ or IHC2+ combined with a negative in situ hybridisation (ISH) test are described as HER2-Low. SG, a novel Trop-2–directed antibody-drug conjugate, is approved for patients (pts) with metastatic triple-negative breast cancer in the second-line or greater setting. In the TROPiCS-02 study, SG demonstrated a 34% reduction in risk of progression or death vs treatment of physician’s choice (TPC) in heavily pretreated, endocrine-resistant HR+/HER2– MBC (Rugo H, et al. ASCO 2022; LBA1001). In this TROPiCS-02 post hoc analysis, we describe SG efficacy in HER2 IHC0 and HER2-Low HR+/HER2– MBC.
Methods
Pts with HR+/HER2– unresectable locally advanced or MBC and 2-4 prior chemotherapy regimens for MBC were randomised 1:1 to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until unacceptable toxicity or disease progression. Primary endpoint was progression-free survival (PFS) per RECIST 1.1 by central review. Pts with known HER2-positive disease were ineligible, with HER2 status (IHC and ISH) assessed locally.
ISH, in situ hybridisation; IHC, immunohistochemistry; mPFS, median progression-free survival; ORR, objective response rate; pts, patients; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.*39 of 117 IHC2+ pts (33%; 14% of all HER2-Low pts) did not have an ISH test result but were assumed to be ISH-negative due to study eligibility criteria (HER2− disease). Similar results were observed when the 39 pts were excluded from the analysis.
Results
In the intent-to-treat (ITT) population and in each treatment arm, 92% of pts were HER2 IHC0 or HER2-Low. Baseline characteristics between HER2 IHC0 and HER2-Low were comparable and similar to that of the ITT population. Median PFS was improved with SG vs TPC in the HER2 IHC0 and HER2-Low groups (HR 0.72, P=0.05 and 0.58, P<0.001, respectively; Table). The safety profile of the subgroups was consistent with that of the overall safety population.
Conclusions
Clinical benefit with SG vs TPC in HER2 IHC0 and HER2-Low HR+/HER2- MBC was consistent with that of the TROPiCS-02 ITT population. SG should be considered an effective treatment option for pts with HR+/HER2- MBC, regardless of HER2 status.
See more from MedicalBrief archives:
‘Practice-changing’ results for breast cancer with Enhertu treatment
Faster breast cancer radiation treatment as effective as long course
Amazon involved in new cancer vaccine clinical trial
Patient’s opinion on cancer treatment often under-valued – Australian study