Characterization of Long-Term Survivors in TOPAZ-1

March 2023, Vol 4, No 1

Results from the primary analysis of TOPAZ-1 were practice changing, establishing a new frontline standard of care for patients with advanced biliary tract cancer (BTC). Initial results after data cutoff demonstrated a significant improvement in overall survival (OS) with the addition of durvalumab to gemcitabine/cisplatin (GemCis) in patients with advanced BTC, with OS curves that persisted during further follow-up. Dr Mohamed Bouattour presented results from an analysis aimed at assessing characteristics, outcomes, and genomic profiles of long-term survivors (LTS) treated with durvalumab plus GemCis or placebo (PBO) plus GemCis in TOPAZ-1.

Patients with advanced BTC in TOPAZ-1 were randomly assigned to receive durvalumab plus GemCis or PBO plus GemCis for up to 8 cycles and then continued durvalumab or PBO until disease progression or toxicity. The post hoc, exploratory analysis was performed from the full analysis set (FAS), which included all randomized participants, and the safety analysis set (SAS). Patients who were LTS survived ≥18 months after randomization (data cutoff: February 25, 2022). Key outcomes included patient and disease characteristics, duration of treatment, objective response rate (ORR), and molecular characterization using FoundationOne panel.


Dr Mohamed Bouattour presented results from an analysis aimed at assessing characteristics, outcomes, and genomic profiles of long-term survivors (LTS) treated with durvalumab plus GemCis or placebo (PBO) plus GemCis in TOPAZ-1.

In total, 153 patients were LTS, and more patients were LTS in the durvalumab plus GemCis group versus patients treated with PBO plus GemCis (88 patients vs 65 patients). Patient characteristics of LTS were consistent compared with characteristics in the FAS, including age, sex, disease classification, and PD-L1 expression. The ORR in LTS was 44.3% with durvalumab plus GemCis versus 33.8% with PBO plus GemCis, which was greater than both groups in the FAS (26.7% for the durvalumab plus GemCis group vs 18.7% in the PBO plus GemCis group). A total of 5 patients who were LTS and were treated with durvalumab plus GemCis achieved a complete response, compared with 2 patients treated with PBO plus GemCis.

The median exposure to study treatment in the LTS group was 11.3 months with durvalumab, 9.7 months with PBO, and 5.5 months with GemCis in both arms, whereas the median exposure to study treatment in the FAS was 7.3 months with durvalumab, 5.8 months with PBO, and 5.1 months with GemCis in both arms. More LTS treated with PBO plus GemCis received subsequent anticancer treatment. The most common subsequent treatment was cytotoxic chemotherapy followed by immunotherapy. Participants in the LTS group and the SAS with any adverse event (AE), any maximum grade 3 or 4 AE, or any serious AE were generally similar.

A total of 441 biomarker-evaluable participants were in the FAS, and 26.1% of these were LTS. The most common alterations were TP53 mutation, CDKN2A/CDKN2B/MTAP loss, KRAS mutation, ARID1A mutation, and SMAD4 mutation. BRCA1/BRCA2 mutations were higher in LTS compared with non-LTS in both treatment arms, suggesting that the prevalence of these mutations may be associated with long-term survival. ERBB2 amplification was more common in LTS treated with PBO plus GemCis, and KRAS and IDH1 mutations were more common in LTS treated with durvalumab plus GemCis versus PBO plus GemCis.


Mutations in BRCA1/BRCA2 may suggest a long-term survival benefit regardless of treatment, and KRAS and IDH1 mutations were more prevalent in LTS treated with durvalumab plus GemCis.

Overall, more LTS were seen in the group treated with durvalumab plus GemCis compared with PBO plus GemCis, and patients treated with PBO were more likely to receive subsequent treatment, which included immunotherapy. Mutations in BRCA1/BRCA2 may suggest a long-term survival benefit regardless of treatment, and KRAS and IDH1 mutations were more prevalent in LTS treated with durvalumab plus GemCis.

Source: Bouattour M, Valle JW, Vogel A, et al. Characterization of long-term survivors in the TOPAZ-1 study of durvalumab or placebo plus gemcitabine and cisplatin in advanced biliary tract cancer. Poster presented at: ASCO Gastrointestinal Cancers Symposium, January 19-21, 2023; San Francisco, CA. Abstract 531.

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