Characteristics of Long-Term Survivors in the TOPAZ-1 Trial

Researchers aimed to assess characteristics, outcomes, and genomic profiles of long-term survivors treated with durvalumab plus gemcitabine/cisplatin (GemCis) or placebo plus GemCis in the TOPAZ-1 trial.

Results from the primary analysis of TOPAZ-1 had a profound impact on clinical practice, creating a new benchmark for treating patients with advanced biliary tract cancer (BTC). Initial findings following the data cutoff showed that the addition of durvalumab to gemcitabine/cisplatin (GemCis) significantly increased overall survival (OS) in patients with advanced BTC, with OS curves that maintained during further follow-up. At the 2023 ASCO Gastrointestinal Cancers Symposium, Mohamed Bouattour, MD, presented results from a TOPAZ-1 analysis conducted to evaluate characteristics, outcomes, and genomic profiles of long-term survivors (LTSs) treated with durvalumab plus GemCis or placebo (PBO) plus GemCis.

Mohamed Bouattour, MD, presented results from a TOPAZ-1 analysis conducted to evaluate characteristics, outcomes, and genomic profiles of long-term survivors (LTSs) treated with durvalumab plus GemCis or placebo (PBO) plus GemCis.

In TOPAZ-1, patients with advanced BTC 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 LTSs had an OS ≥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 a FoundationOne panel.

In total, 153 patients were LTSs, and more patients were LTSs in the durvalumab plus GemCis group versus the PBO plus GemCis group (88 patients vs 65 patients). Patient characteristics of LTSs were consistent compared with characteristics in the FAS, including age, sex, disease classification, and PD-L1 expression. The ORR in LTSs 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 durvalu-

mab plus GemCis group vs 18.7% in the PBO plus GemCis group). A total of 5 patients who were LTSs 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 LTSs 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 LTSs 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 LTSs. The most common alterations were TP53 mutation, CDKN2A/CDKN2B/MTAP loss, KRAS mutation, ARID1A mutation, and SMAD4 mutation. BRCA1/BRCA2 mutations were higher in LTSs compared with non-LTSs in both treatment arms, suggesting that the prevalence of these mutations may be associated with long-term survival. ERBB2 amplification was more common in LTSs treated with PBO plus GemCis, and KRAS and IDH1 mutations were more common in LTSs treated with durvalumab plus GemCis versus PBO plus GemCis.

Overall, more LTSs were seen in the group treated with durvalumab plus GemCis compared with the group treated with PBO plus GemCis, and patients treated with PBO were more likely to receive further treatment, which included immunotherapy. Regardless of therapy, BRCA1/BRCA2 mutations may signal an advantage for long-term survival, while KRAS and IDH1 mutations were more common in LTSs 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.