Durvalumab + chemo maintains OS benefit in advanced biliary tract cancer – AstraZeneca

The addition of durvalumab (Imfinzi) to gemcitabine and cisplatin demonstrated a sustained overall survival (OS) benefit vs chemotherapy alone in patients with unresectable, locally advanced or metastatic biliary tract cancer, according to updated 3-year follow-up data from the phase III TOPAZ-1 study (NCT03875235) presented at the 2024 ESMO Gastrointestinal Cancers Congress.

Findings showed that patients treated with the durvalumab combination (n = 341) experienced a median OS of 12.9 months (95% CI, 11.6-14.1) vs 11.3 months (95% CI, 10.1-12.5) in those treated with placebo plus chemotherapy (n = 344; /HR, 0.74; 95% CI, 0.63-0.87). The 36-month OS rates were 14.6% and 6.9%, respectively (OS rate ratio = 2.12).

“At 36 months, the [OS] rate in the durvalumab plus gemcitabine and cisplatin arm was more than double the survival rate in the placebo plus gemcitabine and cisplatin arm,” lead study author Do-Youn Oh, MD, PhD, stated in a presentation of the data.

Previously reported data from the primary analysis of TOPAZ-1 showed a significant improvement in OS with the addition of durvalumab vs chemotherapy alone, as well as acceptable safety. At the primary analysis, the median OS was 12.8 months (95% CI, 11.1-14.0) for the durvalumab regimen vs 11.5 months (95% CI, 10.1-12.5) for the placebo regimen (HR, 0.80; 95% CI, 0.66-0.97; P = .021).

In September 2022, the FDA approved durvalumab in combination with gemcitabine and cisplatin for the treatment of adult patients with locally advanced or metastatic biliary tract cancers, based on prior data from TOPAZ-1.

The multicenter, global, double-blind, randomized study enrolled patients with unresectable, locally advanced or metastatic biliary tract cancer. Patients with unresectable or metastatic disease at diagnosis needed to be previously untreated. Patients with recurrent disease were allowed if recurrence occurred more than 6 months after curative surgery or the completion of adjuvant therapy. An ECOG performance status of 0 or 1 was also required. Eligible patients were randomly assigned 1:1 to receive 1500 mg of durvalumab once every 3 weeks plus up to 8 cycles of gemcitabine and cisplatin, followed by 1500 mg of durvalumab once every 4 weeks until disease progression; or placebo one every 3 weeks plus up to 8 cycles of chemotherapy, followed by placebo once every 4 weeks until disease progression. Notably, the primary end point of the study was OS.

Additional data showed that in patients who achieved a complete response (CR), partial response (PR), or stable disease (SD), the median OS was 14.6 months (95% CI, 13.3-16.6) in the durvalumab arm (n = 285) vs 12.8 months (95% CI, 11.6-13.7) in the placebo arm (n = 281). The 36-month OS rate in patients with disease control was 17.0% vs 7.6% for the durvalumab and placebo regimens, respectively. In patients who had a best objective response (BOR) of CR or PR, the 36-month OS rate was 31.9% for the durvalumab arm (n = 91) vs 15.6% for the placebo arm (n = 64). In patients who had a BOR of SD, the 36-month OS rates were 9.8% for the durvalumab arm (n = 194) and 5.1% for the placebo arm (n = 217). These respective rates were 4.5% and 6.9% in those who had progressive disease in the durvalumab (n = 22) and placebo (n = 29) arms.

Oh and colleagues also analyzed outcomes for patients who achieved extended long-term survival, defined as being alive at least 30 months after randomization. “Baseline characteristics [in the population of extended long-term survivors] were generally consistent with the full-analysis set [FAS],” Oh said. “All clinically relevant subgroups were represented in the extended long-term survival [analysis]. No single subgroup drove long-term survivorship.”

In patients who achieved extended long-term survival, the objective response rates (ORRs) were 55.2% for the durvalumab arm (n = 58) and 40.0% for the placebo arm (n = 30). In the FAS, the respective ORRs were 26.7% and 18.7%. A higher proportion of patients had extended long-term survival in the durvalumab group (17.0%) vs the placebo group (8.7%). In all patients in the FAS (n = 658), 46.0% of patients underwent any subsequent anticancer therapy at the time of the primary analysis vs 54.9% of patients at the 3-year OS analysis; these subsequent therapies included chemotherapy (primary analysis, 44.8%; 3-year OS analysis, 54.2%), immunotherapy (2.8%; 5.5%), and targeted therapy (4.1%; 8.2%).

Data from the 3-year OS analysis showed that in the extended long-term survival group , 54.6% of patients in the durvalumab arm underwent any subsequent anticancer therapy vs 83.3% of those treated in the placebo arm. Subsequent therapies included chemotherapy (durvalumab arm, 51.7%; placebo arm, 80.0%), immunotherapy (6.9%; 23.3%), and targeted therapy (19.0%; 26.7%).

Regarding safety , no meaningful changes in the rates of serious adverse effects (AEs) or serious treatment-related AEs were reported in the updated analysis. At the time of the 3-year OS analysis, 13 patients in the durvalumab group and none in the placebo group remained on study treatment. The median duration of treatment was also longer for patients who received the durvalumab combination in the extended long-term survival group (17.8 months) vs those who received it in the FAS group (7.3 months).In all evaluable patients from the FAS at the 3-year OS analysis, 48.8% of patients in the durvalumab arm (n = 338) and 44.4% of patients in the placebo arm (n = 342) experienced a serious AE; the rates of serious AEs possibly related to study treatment were 15.4% vs 17.3%, respectively. AEs led to the discontinuation of durvalumab in 6.2% of patients in the experimental arm; 5.3% of patients in the control arm discontinued placebo due to AEs. The median duration of durvalumab was 7.3 months (range, 0.1-50.9) vs 5.8 months (range, 0.2-26.6) for placebo.

In the extended long-term survival group , 32.8% of patients in the durvalumab arm vs 36.7% of patients in the placebo arm experienced a serious AE. The rates of serious AEs possibly related to treatment were 8.6% vs 10.0%, respectively. AEs led to discontinuation of durvalumab and placebo in 5.2% and 3.3% of patients, respectively. The median duration of durvalumab therapy was 17.8 months (range, 3.4-50.9) vs 10.5 months (range, 2.2-28.4).