Low ranges of circulating tumor DNA (ctDNA) could point out an extended recurrence-free interval in sufferers with triple-negative breast most cancers.
Amongst sufferers with triple-negative breast most cancers (TNBC), circulating tumor DNA (ctDNA) was detected most incessantly on the preliminary check and at six months or much less after therapy, which was in line with the illness’s typical sample of early recurrence charges in TNBC, in keeping with knowledge from the terminated part 3 ZEST trial offered on the 2024 San Antonio Breast Most cancers Symposium (SABCS).
The ZEST trial was thought-about the primary part 3 trial of minimal-residual illness (MRD)–guided remedy in breast most cancers. Nonetheless, the trial was terminated early due to low randomization charges.
This “largely mirrored broad entry standards that allowed a comparatively massive variety of low-risk sufferers to enroll that resulted in a low price of ctDNA detection,” Dr. Nick Turner, head of Ralph Lauren Centre for Breast Most cancers Analysis Breast Unit and Scientific Analysis director at The Royal Marsden and Institute of Most cancers Analysis NIHR Biomedical Analysis Centre, London, defined in the course of the presentation.
In an exploratory evaluation, knowledge demonstrated that the recurrence-free interval could also be longer in sufferers with low ctDNA ranges at baseline. Findings confirmed that sufferers with TNBC handled with placebo (13 sufferers) who had excessive ctDNA ranges at baseline had a median illness recurrence of three.2 months in contrast with 5.7 months in these handled with Zejula (niraparib; seven sufferers). Moreover, sufferers handled with placebo (9 sufferers) who had low ctDNA ranges at baseline had a median illness recurrence of seven.4 versus 15.9 months in sufferers handled with Zejula (11 sufferers).
Glossary:
Finish of definitive therapy (EODT): completion of main most cancers remedy.
Minimal residual illness (MRD): small quantities of most cancers remaining after therapy.
Recurrence-free interval: time that the most cancers stays undetected after therapy.
Median recurrence-free interval within the placebo group was 5.4 months and 11.4 within the Zejula group.
Extra Efficacy Information
Total, ctDNA was detected in 6.7% of sufferers inside three months following the top of definitive therapy (EODT), 5.2% between three to 6 months, 2.5% between six to 9 months, 3.1% between 9 to 12 months and 1.8% past 12 months. The research included 147 sufferers, with the bulk having TNBC (135 sufferers) and a smaller subset having HR–constructive breast most cancers (12 sufferers).
Amongst sufferers with TNBC, 60% of ctDNA-positive circumstances have been recognized inside six months post-EODT (81 sufferers), 29.7% have been recognized between six to 12 months (40 sufferers) and 10.4% have been recognized after 12 months (14 sufferers). For HR-positive sufferers, 50% of ctDNA-positive circumstances have been detected inside six months (6 sufferers), 16.7% between six to 12 months (2 sufferers) and 33.3% past 12 months (4 sufferers). Nonetheless, the researchers famous that the information for HR-positive sufferers have been restricted because of the small pattern dimension.
ctDNA detection was related to illness stage (stage 3, 13.7%) pathological consequence from neoadjuvant therapy (non-pathologic full response, 13.7%), systemic anti-cancer remedy (neoadjuvant plus adjuvant, 12.8%) and prior remedy Xeloda, (capecitabine) 13.5%).
Trial Design and Affected person Traits
Sufferers have been eligible for the part 3 scientific trial if that they had phases 1 to three breast most cancers, TNBC no matter BRCA standing or tumor BRCA1 or 2 pathogenic variant standing HR-positive, HER2-negative illness, accomplished prior commonplace healing intent remedy together with endocrine remedy for HR-positive most cancers and adjuvant Keytruda (pembrolizumab) for TNBC and had no scientific indicators of recurrence. Sufferers who had acquired neoadjuvant chemotherapy and whose tumors confirmed no response have been excluded from the research.
Sufferers entered ctDNA surveillance (1,901 sufferers), 147 sufferers have been ctDNA constructive and 96 entered screening. Sufferers have been then randomly assigned (40 sufferers) to obtain placebo (22 sufferers) or Zejula (18 sufferers). The trial was unable to judge the impact of Zejula veruss placebo due to its termination.
Concerning baseline traits, the median age was 59 years within the Zejula group and 53.5 years within the placebo group. Illness varieties included TNBC (94.4%; 86.4%, respectively) and HR-positive illness (5.6%; 13.6%); centralized BRCA standing included mutant (5.6%; 22.7%) and wild kind (94.4%; 77.3%). Node standing was constructive (66.7%; 63.6%), unfavorable (33.3%; 31.8%) or not out there (0%; 4.5%). Sufferers had stage 1 (5.6%; 22.7%), stage 2 (33.3%; 13.6%) or stage 3 (61.1%; 63.6%) illness. Systemic anticancer therapies acquired by sufferers included neoadjuvant (27.8%; 22.7%), adjuvant (11.1%; 31.8%) or neoadjuvant plus adjuvant (61.1%; 45.5%). Prior therapies included Xeloda (61.1%; 31.8%), endocrine remedy (0%; 13.6%), Keytruda (0%; 9.1%) and platinum-based chemotherapy (33.3%; 40.9%).
The first finish level was initially disease-free survival, nevertheless it was modified to security and tolerability of Zejula when enrollment stopped. Turner famous that the trial was not powered to judge the impact of Zejula versus placebo given early termination; nevertheless, recurrence-free interval was numerically longer with Zejula. Turner didn’t current on the protection or tolerability on the symposium.
Reference:
“Circulating tumor DNA surveillance in ZEST, a randomized, part 3, double-blind research of niraparib or placebo in sufferers with triple-negative breast most cancers or HER2-, BRCA-mutated breast most cancers with molecular residual illness after definitive remedy.” By Dr. Nick Turner, et al., 2024 San Antonio Breast Most cancers Symposium.
For extra information on most cancers updates, analysis and training, don’t overlook to subscribe to CURE®’s newsletters right here.
