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Trodelvy plus Keytruda may maintain quality of life and slow physical decline in metastatic triple-negative breast cancer.
Among patients with previously untreated, PD-L1-positive metastatic triple-negative breast cancer (mTNBC), treatment with Trodelvy (sacituzumab govitecan) plus Keytruda (pembrolizumab) has been shown to possibly lead to maintained quality of life (QOL).
Patient reported outcomes (PROs) from the phase 3 ASCENT-04/KEYNOTE-D19 study were presented at the 2025 ESMO Congress, showing the combination may potentially provide a delay in the onset of physical decline.
“[Trodelvy] plus [Keytruda] maintained overall QOL,” Dr. Evandro de Azambuja, head of the Medical Support Team at the Jules Bordet Institute, Brussels, Belgium, said during a presentation of the data. “Patients reported reduced symptom burden and improved functioning in multiple domains. These data complement the clinically meaningful improvement in progression-free survival and support this treatment regimen as a potential new standard of care for patients with PD-L1–positive mTNBC.”
Progression-free survival (PFS): This is the length of time a person lives while taking a cancer treatment during which the cancer does not get worse or grow.
Duration of response (DOR): This is the time span that the cancer remains significantly shrunk or completely gone after a treatment has successfully worked.
Neutropenia: This is a condition where you have an abnormally low number of neutrophils, which are a type of white blood cell important for fighting infection.
Time to deterioration in physical functioning was comparable between the Trodelvy plus Keytruda and chemotherapy plus Keytruda groups (median, three months versus 3.5 months).
However, the sensitivity analysis showed prolonged time to first deterioration with the Trodelvy regimen compared with chemotherapy (median, 9.3 months versus 6.9 months). Time to confirmed deterioration through the sensitivity analysis also showed a prolonged duration of 8.8 months with Trodelvy plus Keytruda versus 5.7 months with Keytruda plus chemotherapy.
“Both sensitivity analyses consistently showed that [Trodelvy] plus [Keytruda] has a numerically longer time to deterioration and may delay the onset of decline in physical functioning,” de Azambuja said. “If you look into different domains, quality of life was maintained across different domains.”
According to time to deterioration, emotional functioning (median, 9.3 months versus 4.9) and pain (median, 4.3 versus 3.2) were favored with Trodelvy plus Keytruda compared with Keytruda plus chemotherapy.
“There was worsening of symptoms such as nausea/vomiting and diarrhea, which are consistent with the safety profile of the [Trodelvy] plus [Keytruda] group in the study and can be managed by following established guidelines,” de Azambuja said.
Lastly, from baseline to EORTC QLQ-C30 scores, the Trodelvy regimen was more favorable compared with the chemotherapy regimen for physical (least squares mean change, 2.45), role (3.34), and emotional (4.07) functioning, as well as pain (-5.39) and insomnia (-4.59).
According to de Azambuja, approximately 50% of patients with mTNBC who receive first-line treatment do not receive second-line therapy, which includes a substantial deterioration in QOL with each line of therapy. He added that frontline therapy may be an important opportunity to control disease without worsening QOL.
“Patient-reported outcome will provide insight from impact on treatments including symptom burden and functional status,” de Azambuja said.
The investigators evaluated QOL as a secondary end point of the trial, including time to deterioration in physical functioning and time to deterioration in the role of functioning, GHS/QOL, pain and fatigue.
Patient-reported outcome assessments occurred at baseline, day 1 of all cycles and the end of treatment. Questionnaires were completed in about 70% of treatment arms, de Azambuja noted.
Baseline EORTC QLQ-C30 domain scores were consistent between treatment groups and with general population scores for most domains.
The randomized, open-label, phase 3 trial evaluated the efficacy of Trodelvy in combination with Keytruda versus Keytruda plus physician’s choice of chemotherapy in patients with previously untreated, locally advanced, inoperable or metastatic TNBC whose tumors expressed PD-L1 with a CPS of 10 or greater. Four hundred and forty-three patients were randomized to receive either Trodelvy plus Keytruda (221 patients) or Keytruda plus chemotherapy (222 patients).
The Trodelvy regimen reduced the risk for disease progression by 35% after a median follow-up of 14 months. Further, median duration of response was 16.5 months for Trodelvy plus Keytruda compared with 9.2 months with Keytruda plus chemotherapy.
Of note, the most frequent grade 3 (severe) or higher treatment-emergent side effects with the Trodelvy regimen were neutropenia (43%) and diarrhea (10%) and with the chemotherapy regimen were neutropenia (45%), anemia (16%) and thrombocytopenia (14%).
“The primary analysis of ASCENT-04 showed a statistically significant and clinically important improvement in median progression-free survival with [Trodelvy] plus [Keytruda] as first-line treatment for untreated PD-L1–positive metastatic triple-negative breast cancer,” de Azambuja said.
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