Durvalumab gecombineerd met paclitaxel toont activiteit bij mTNBC, toevoeging van capivasertib of oleclumab levert geen extra voordeel op
In de fase Ib/II BEGONIA-platformstudie werden 87 patiënten met onbehandeld lokaal gevorderd of metastatisch triple-negatief borstkanker behandeld met durvalumab plus paclitaxel, met of zonder capivasertib of oleclumab.
De bevestigde objectieve responsratio bedroeg 56,5% voor de durvalumab-paclitaxelcombinatie, 54,8% voor de capivasertib-arm en 51,5% voor de oleclumab-arm. Ernstige bijwerkingen (graad 3/4) traden vaker op bij toevoeging van capivasertib (80,6%) dan bij de andere behandelregimes.
Deze bevindingen bevestigen de activiteit van durvalumab gecombineerd met chemotherapie, maar tonen aan dat toevoeging van capivasertib of oleclumab geen substantieel extra voordeel biedt, wat verdere ontwikkelingen in de eerste-lijn behandeling van mTNBC kan sturen.
Abstract (original)
PURPOSE: Triple-negative breast cancer (TNBC) is a heterogeneous disease with high recurrence rates and poor prognosis, often requiring multiple therapies. BEGONIA was a phase Ib/II, multiarm, platform study evaluating the safety and efficacy of first-line treatment combinations with durvalumab (anti-PD-L1 antibody) for locally advanced unresectable/metastatic TNBC (mTNBC; NCT03742102). Here, we report results of three treatment arms. PATIENTS AND METHODS: Eligible female participants (≥18 years with untreated, unresectable, locally advanced/mTNBC) received durvalumab plus paclitaxel or were randomized to this treatment in combination with capivasertib (pan-AKT inhibitor) or oleclumab (anti-CD73 antibody). The primary objective was safety and tolerability; secondary endpoints included objective response rate (ORR). RESULTS: Twenty-three patients received durvalumab plus paclitaxel, 31 capivasertib combination, and 33 oleclumab combination. Maximum grade 3/4 adverse events occurred in 10/23 (43.5%), 25/31 (80.6%) and 8/33 (24.2%) patients in the durvalumab plus paclitaxel, capivasertib-combination, and oleclumab-combination arms, respectively. Confirmed ORR (95% confidence interval) was 56.5% (34.5-76.8) with durvalumab plus paclitaxel, 54.8% (36.0-72.7) with capivasertib combination, and 51.5% (33.5-69.2) with oleclumab combination. Responses were observed across biomarker subgroups, including PD-L1, PIK3CA/AKT1/PTEN alterations, and CD73, with a trend for improved activity in the PD-L1-positive subgroups. CONCLUSIONS: These findings support the clinical activity and tolerability of durvalumab plus paclitaxel in locally advanced unresectable/mTNBC, as expected for an immune checkpoint inhibitor in combination with chemotherapy. Addition of capivasertib or oleclumab to this treatment combination showed no substantial additional benefit. PD-L1 expression was associated with enhanced antitumor activity across all arms.
Dit artikel is een samenvatting van een publicatie in Clinical cancer research : an official journal of the American Association for Cancer Research. Voor het volledige artikel, alle details en referenties verwijzen wij u naar de oorspronkelijke bron.
Lees het volledige artikelDOI: 10.1158/1078-0432.CCR-25-4417