Abstract 293P
Background
The TOPAZ-1 phase 3 trial demonstrated a survival advantage with the anti-PD-L1 durvalumab, when used with gemcitabine and cisplatin for patients with advanced biliary tract cancer (BTC). To gain a broader understanding of the efficacy and tolerability of this combination, we performed a worldwide multicenter retrospective analysis to investigate the efficacy and safety of this new first-line standard treatment in a real-word setting.
Methods
The analyzed population included patients (pts) with unresectable, locally advanced or metastatic BTC treated with durvalumab, gemcitabine and cisplatin at 38 sites from 10 countries in Europe, United States, and Asia. The primary endpoint of the study was OS.
Results
618 pts were enrolled.At data cutoff(January 20, 2024),the median duration of follow-up was 8.5 months(95% CI: 7.9-9.4), 52.9% discontinued the treatment due to PD,and 30.4% died. Patient characteristics are reported in the table. Median OS was 15.1 months (95% CI 13.4-29.1) and median PFS 8.1 months (95% CI 7.5-8.7).ORR was 31.7% (CR 2.5%, PR 29.6%), SD 46.7%, and DCR 78.8%. Any grade AEs occurred in 92.8% of pts. Grade 3-4 AEs in 46.0%. The most common AEs were fatigue (55.1%), anemia (48.7%), neutropenia (46.0%), and thrombocytopenia (38.5%). The rate of immune-mediated AEs (imAEs) was 19.7%. Grade 3-4 imAEs occurred in 2.5% of the patients. CEA normal value (p=0.0009,HR:0.66),ECOG PS 0 (p=0.0014,HR:0.67), locally advanced disease (p=0.0010,HR:0.47), and NLR <3 (p=0.0002,HR:0.53) were correlate with better outcome. Table: 293P
| Characteristic | N (%) N=618 |
| Gender | |
| Male | 328 (53.1) |
| Female | 290 (46.9) |
| Age at first-line therapy years | 67 (range 29-89) |
| Primary tumor site | |
| Intrahepatic | 330 (53.4) |
| Extrahepatic | 160 (25.9) |
| Gallbladder | 128 (20.7) |
| Previous surgery Yes No | 168 (27.2) 450 (72.8) |
| Disease status | |
| Locally advanced | 142 (23.0) |
| Metastatic | 476 (77.0) |
| ECOG PS | |
| 0 | 302 (48.9) |
| >0 | 316 (51.1) |
| CA 19-9 median (range) UI/mL | 103 (0.6-400000) |
| Within normal kevels | 189 (32.0) |
| >Normal levels | 395 (63.9) |
| Not reported | 34 (4.1) |
| CEA median (range) ng/mL | 3.1 (0.2-30340) |
| Within normal levels | 314 (50.8) |
| >Normal levels | 244 (39.5) |
| Not reported | 60 (9.7) |
Conclusions
The results reported in this first worldwide real-world analysis mostly confirmed the results achieved in the TOPAZ-1 trial and further support the combination of gemcitabine plus cisplatin and durvalumab as a standard of care for the first-line treatment of pts with advanced BTC.
Legal entity responsible for the study
San Rafaele hospital.
Funding
Has not received any funding.
Disclosure
L. Rimassa: Financial Interests, Personal, Advisory Board, Consulting and advisory role: AbbVie, AstraZeneca, Basilea, Bayer, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, Bayer, BMS, Incyte, Ipsen, Roche, Servier; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Exelixis, Incyte, Ipsen, Nerviano Medical Sciences, Roche, Servier, Agios, Eisai, FibroGen, Lilly, MSD, Roche, Servier; Financial Interests, Institutional, Invited Speaker, National (Italian) coordinating PI: AstraZeneca, BeiGene, Zymeworks; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Invited Speaker, European PI: AstraZeneca; Non-Financial Interests, Leadership Role, Treasurer: ILCA; Non-Financial Interests, Leadership Role, Co-chair: EORTC GITCG HB/NET Task Force; Non-Financial Interests, Other, Special Expert Clinical Trials Europe: NCI HB Task Force. All other authors have declared no conflicts of interest.