Following results from a phase III trial, the FDA granted accelerated approval to pembrolizumab (Keytruda), in combination with chemotherapy, for metastatic or locally recurrent unresectable triple-negative breast cancer (TNBC).
The PD-1-directed immune checkpoint inhibitor is indicated for TNBC patients with a PD-L1 combined positive score (CPS) ≥10, based on findings from KEYNOTE-355 presented at the American Society of Clinical Oncology virtual meeting.
About 38% of patients in the 847-person study had PD-L1 expression levels reaching CPS ≥10, and median progression-free survival (PFS) in this subgroup improved from 5.6 months with chemotherapy plus placebo to 9.7 months with chemotherapy plus pembrolizumab (HR 0.65, 95% CI 0.49-0.86, one-sided P=0.0012).
Overall survival (OS) data, however, were still immature at the time of the analysis.
“Notably, in KEYNOTE-355, Keytruda was combined with three different chemotherapy regimens: paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin,” Hope Rugo, MD, of the University of California San Francisco, said in a press release from drugmaker Merck.
The approval “gives physicians an important new option for appropriate patients,” she added.
The overall response rate (ORR) in the pembrolizumab arm was 53%, including complete responses in 17%, as compared to an ORR of 40% in the control arm, with complete responses in 13%. Median duration of response was 19.3 months versus 7.3 months, respectively.
Below are other highlights of important developments in the management of TNBC in 2020.
FDA Warns on Tecentriq-Paclitaxel Combo in Breast Cancer
Results from another phase III study involving a different immunotherapy-chemotherapy combination for the first-line treatment of metastatic TNBC led the FDA to issue a safety alert.
The agency warned on using atezolizumab (Tecentriq), a PD-L1 immune checkpoint inhibitor, in combination with paclitaxel after the randomized IMpassion131 trial suggested a potential survival detriment.
For background, the combination of atezolizumab plus a different chemotherapy with a similar name — nab-paclitaxel (Abraxane) — was granted accelerated approval last year in patients with metastatic or locally advanced, unresectable TNBC whose tumors express PD-L1, based on positive PFS data from IMpassion130. OS favored the combination as well (HR 0.62, 95% CI 0.45-0.86).
But in IMpassion131, results from which were presented at the European Society for Medical Oncology (ESMO) virtual congress, paclitaxel plus atezolizumab failed to significantly improve PFS over paclitaxel and placebo in PD-L1-positive metastatic TNBC patients, and OS was numerically worse with paclitaxel-atezolizumab in both the PD-L1-positive subgroup and the total population.
In short, the agency warned against replacing nab-paclitaxel with paclitaxel in routine clinical practice for TNBC patients receiving atezolizumab.
“FDA will review the findings of IMpassion131 and will communicate new information regarding the IMpassion131 results and any potential changes to prescribing information,” the agency stated. “FDA is also evaluating the use of atezolizumab and paclitaxel in ongoing clinical trials for breast cancer and will recommend additional changes as appropriate.”
Discussing the three trials (KEYNOTE-355, IMpassion130, and IMpassion131) at ESMO, Lisa Carey, MD, of the University of North Carolina in Chapel Hill, said atezolizumab plus nab-paclitaxel remains her first choice based on both the PFS and OS advantage.
“Adding atezolizumab to paclitaxel did not improve PFS or OS, for reasons that are as yet undetermined,” she said. “Pembrolizumab plus chemotherapy met the PFS endpoint with a similar hazard ratio as atezolizumab, but we don’t have overall survival data yet.”
ADC Nabs Approval, Boosts Survival in Metastatic TNBC
The antibody-drug conjugate (ADC) sacituzumab govitecan (Trodelvy) also gained accelerated approval in 2020 for treating TNBC in patients who have received at least two prior therapies for metastatic disease.
Sacituzumab govitecan is a conjugate product, linking a monoclonal antibody directed against trophoblast cell-surface antigen (Trop)-2 to a topoisomerase inhibitor. Trop-2 is highly expressed in breast cancer. The approval came based on a single-arm trial in which one-third of patients showed responses.
Further results on the drug in TNBC came from phase III findings from the ASCENT trial, also presented at ESMO, showing improvement over physician’s choice of chemotherapy in the third-line setting.
The trial met its primary endpoint, demonstrating an improvement in median PFS in patients without brain metastases and whose disease progressed on at least two earlier lines of therapy, from 1.7 months with single-agent chemotherapy to 5.6 months with sacituzumab govitecan (HR 0.41, 95% CI 0.32-0.52, P<0.0001), reported Aditya Bardia, MD, MPH, of Harvard Medical School in Boston.
Median OS was also superior with sacituzumab govitecan, improving from 6.7 months with chemotherapy to 12.1 months with sacituzumab govitecan (HR 0.48, 95% CI 0.38-0.59, P<0.0001).
“The clinical benefit here confirms the use of sacituzumab govitecan as a standard therapy for patients with pretreated metastatic triple-negative breast cancer,” Bardia said.
Can Screening Eliminate Survival Disparities in TNBC?
In a single-center study, OS differences between Black and white women with TNBC appeared to vanish when tumors were detected by routine screening.
Among Black patients diagnosed with TNBC, 4-year OS was significantly worse, at 59.1% without screening versus 93.2% for screen-detected tumors (P<0.001), Lisa Newman, MD, MPH, of Weill Cornell Medicine in New York City, and colleagues reported in JAMA Surgery.
For white women in the study, no significant 4-year OS difference was found between patients whose cancers were detected without screening and those with screen-detected TNBCs (74.8% vs 87.5%, respectively).
The retrospective study examined outcomes among 106 Black women and 87 white women in the Henry Ford Health System database.
This study “argues for increased screening for all women and highlights the need for increased efforts to screen traditionally underserved populations,” Laurie Margolies, MD, a professor of radiology at Icahn School of Medicine at Mount Sinai in New York City, told MedPage Today.
But the study doesn’t explain the higher incidence of TNBC among Black women, noted Veronica Jones, MD, a breast surgeon at City of Hope in Duarte, California. “The question at hand is why there is an increased incidence of triple-negative subtypes in African-American women and if there is any screening/prevention tool to address the disparity in incidence,” she said.
Other TNBC developments in 2020:
Add-On Keytruda Doubles pCR Rate in Early Breast Cancer
Anti-PD-L1 Plus PARP Inhibitor Ups Response in Breast Cancer
High Conversion Rate for Conservative Therapy in TNBC
New Clue to Anti-PD-L1 Activity in Breast Cancer?
Two Regimens Active in BRCA+ Triple-Negative Breast Cancer
Win for PARP Inhibitor in BRCA Breast Cancer
Could High-Dose Chemo Return for Select Breast Cancers?
Last Updated December 03, 2020
Source: MedicalNewsToday.com
