Durvalumab–Chemotherapy Approach Supported For Operable Muscle-Invasive UC

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Patients with operable muscle-invasive urothelial carcinoma may benefit from use of durvalumab before and after surgery in combination with neoadjuvant chemotherapy, say the SAKK 06/17 investigators. 

As reported at the 2021 Genitourinary Cancers Symposium, the phase II open-label trial included 58 patients, aged a median 67.5 years old, with T2–T4a, N0/N1 disease who were candidates for cisplatin chemotherapy and surgery. The majority (97%) of patients had bladder disease and just 17% had a positive lymph node. 

Neoadjuvant treatment consisted of four cycles of cisplatin 70 mg/m2 on day 1 of each 21-day cycle plus gemcitabine 1000 mg/m2 on days 1 and 8, with four cycles of durvalumab begun on day 1 of chemotherapy cycle 2 at a dose of 1500 mg every 3 weeks. 

Most (98%) patients completed cisplatin and gemcitabine treatment according to protocol and 95% of patients received all four durvalumab doses, although 24% required a dose delay of the PD-L1 inhibitor, reported presenting author Richard Cathomas, from Cantonal Hospital Graubunden in Switzerland. 

Fifty-three patients were suitable candidates for radical cystectomy (n=51) or nephroureterectomy (n=2), with an R0 margin achieved in all but one patient. Four patients refused radical surgery and one patient was considered to have inoperable disease, said the presenter. 

After surgery patients continued with adjuvant durvalumab 1500 mg every 4 weeks for up to 10 cycles, he explained. 

A pathological complete response (ypT0, N0) was achieved by 34% of patients who underwent surgery and 60% achieved a pathological response (<ypT2). 

These SAKK 06/17 rates “confirm results” from the similar phase II BLASST-1 trial of nivolumab plus cisplatin–gemcitabine and the HOG trial of pembrolizumab and cisplatin–gemcitabine, Richard Cathomas commented. 

The full safety analysis of 60 patients indicated that treatment-related adverse events at grade 1, 2, 3 and 4 occurred in 8%, 22%, 43% and 25% of participants, respectively, while durvalumab-related side effects among the 58 patients who had received at least one dose of the PD-L1 inhibitor occurred in 19%, 26%, 12% and 2%, respectively. 

Postoperative complications at Clavien-Dindo grade IIIa or worse occurred in 34% of patients, which the presenter said was “comparable” to the rate reported for the PURE-01 trial of neoadjuvant pembrolizumab before radical cystectomy for muscle-invasive urothelial bladder carcinoma. 

“Neoadjuvant durvalumab plus cisplatin–gemcitabine is feasible and can be completed in vast majority of patients”, he summarised, adding that the “triple combination is safe without unexpected toxicities.” 

Richard Cathomas concluded that the final primary endpoint results of 2-year event-free survival are expected in the first quarter of 2022 and that “extensive translational research projects are underway” looking at both tumour and patient factors associated with response. 

Reference 

Cathomas R, Rothschild S, Hayoz S, et al. Safety and efficacy of perioperative cisplatin/gemcitabine (cis/gem) and durvalumab (durva) for operable muscle-invasive urothelial carcinoma (MIUC): SAKK 06/17. J Clin Oncol 2021;39:(suppl 6; abstr 430). DOI:10.1200/JCO.2021.39.6_suppl.430