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Clinical Trial
. 2023 Nov 20;41(33):5131-5139.
doi: 10.1200/JCO.23.00363. Epub 2023 Aug 17.

Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17

Richard Cathomas  1 , Sacha I Rothschild  2   3 , Stefanie Hayoz  4 , Lukas Bubendorf  5 , Berna C Özdemir  6 , Bernhard Kiss  7 , Andreas Erdmann  3 , Stefanie Aeppli  8 , Nicolas Mach  9 , Räto T Strebel  10 , Boris Hadaschik  11 , Dominik Berthold  12 , Hubert John  13 , Deborah Zihler  14 , Mathias Schmid  15 , Ilaria Alborelli  5 , Martina Schneider  4 , Jana Musilova  4 , Martin Spahn  7   16   17 , Ulf Petrausch  18
Affiliations
Clinical Trial

Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17

Richard Cathomas et al. J Clin Oncol. .

Abstract

Purpose: The integration of immunotherapy in the perioperative setting of muscle-invasive urothelial carcinoma (MIUC) appears promising. SAKK 06/17 investigated the addition of neoadjuvant durvalumab to gemcitabine/cisplatin (GC) chemotherapy followed by radical surgery and adjuvant checkpoint inhibition with durvalumab.

Patients and methods: SAKK 06/17 was an investigator-initiated, open-label, single-arm phase II study including cisplatin-fit patients with stage cT2-T4a cN0-1 operable MIUC. Four cycles of neoadjuvant GC in combination with four cycles of durvalumab (start with GC cycle 2) were administered, followed by radical surgery. Adjuvant durvalumab was given for 10 cycles. The primary end point was event-free survival (EFS) at 2 years.

Results: Sixty one patients were accrued at 12 sites. The full analysis set consisted of 57 patients, 54 (95%) had bladder cancer. Median follow-up was 40 months. The primary end point was met, with EFS at 2 years of 76% (one-sided 90% CI [lower bound], 67%; two-sided 95% CI, 62 to 85). EFS at 3 years was 73% (95% CI, 59 to 83). Complete pathologic response in resected patients (N = 52) was achieved in 17 patients (33%), and 31 (60%) had pathologic response <ypT2 ypN0. Overall survival (OS) was 85% (95% CI, 72 to 92) at 2 years and 81% (95% CI, 67 to 89) at 3 years. Grade 3 and 4 treatment-related adverse events (TRAEs) during neoadjuvant treatment occurred in 42% and 25%, respectively. TRAEs related to adjuvant durvalumab were grade 3 in 5 (11%) and grade 4 in 2 (4%) patients.

Conclusion: The addition of perioperative durvalumab to the standard of care for patients with resectable MIUC results in a high EFS and OS at 2 years.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Ulf Petrausch

Consulting or Advisory Role: BMS (Inst), Roche (Inst), MSD (Inst), AstraZeneca (Inst)

Research Funding: Roche (Inst), AstraZeneca (Inst), Pfizer (Inst), BMS (Inst), MSD (Inst)

Patents, Royalties, Other Intellectual Property: ImmOs

Expert Testimony: BMS

Travel, Accommodations, Expenses: Janssen

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Flow diagram. SAE, serious adverse event.
FIG 2.
FIG 2.
Kaplan-Meier curves for EFS and OS. EFS, event-free survival; OS, overall survival.
FIG 3.
FIG 3.
Kaplan-Meier curves for EFS on the basis of (A, B) pathologic T stage and (C) pathologic N stage. EFS, event-free survival; N stage, node stage; T stage, tumor stage.
FIG A1.
FIG A1.
Kaplan-Meier curves for EFS on the basis of (A) PD-L1 overexpression, (B) MTAP proficiency status, and (C) SLFN11 positivity. EFS, event-free survival; MTAP, methylthioadenosine phosphorylase; SLFN11, Schlafen 11.
See this image and copyright information in PMC

References

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