TY - JOUR
T1 - Survival after neoadjuvant/induction combination immunotherapy vs combination platinum-based chemotherapy for locally advanced (Stage III) urothelial cancer
AU - Einerhand, Sarah M. H.
AU - van Dijk, Nick
AU - van Dorp, Jeroen
AU - de Feijter, Jeantine M.
AU - van Montfoort, Maurits L.
AU - van de Kamp, Maaike W.
AU - Schaake, Eva E.
AU - Boellaard, Thierry N.
AU - Hendricksen, Kees
AU - van der Heijden, Michiel S.
AU - van Rhijn, Bas W. G.
N1 - Funding Information: Michiel S. van der Heijden has received research support from Bristol‐Myers Squibb, AstraZeneca, 4SC and Roche and consultancy fees from Bristol‐Myers Squibb, Merck, Merck Sharp & Dohme, Roche, AstraZeneca, Seattle Genetics, Pfizer and Janssen (all paid to the Netherlands Cancer Institute). Bas W. G. van Rhijn received consultancy fees from AstraZeneca and Ferring (all paid to the Netherlands Cancer Institute). No other authors have disclosures relevant to this work. Funding Information: We would like to thank Marja van Rijn (office manager at The Netherland Cancer Institute—Antoni van Leeuwenhoek Hospital) for help verifying the survival status of patients included in our study. We would also like to thank Vincent van der Noort (bio-statistician at The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital) for help with the inverse probability of treatment weighting (IPTW)-adjusted analyses. Publisher Copyright: © 2022 UICC.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Despite treatment with cisplatin-based chemotherapy and surgical resection, clinical outcomes of patients with locally advanced urothelial carcinoma (UC) remain poor. We compared neoadjuvant/induction platinum-based combination chemotherapy (NAIC) with combination immune checkpoint inhibition (cICI). We identified 602 patients who attended our outpatient bladder cancer clinic in 2018 to 2019. Patients were included if they received NAIC or cICI for cT3-4aN0M0 or cT1-4aN1-3M0 UC. NAIC consisted of cisplatin-based chemotherapy or gemcitabine-carboplatin in case of cisplatin-ineligibility. A subset of patients (cisplatin-ineligibility or refusal of NAIC) received ipilimumab plus nivolumab in the NABUCCO-trial (NCT03387761). Treatments were compared using the log-rank test and propensity score-weighted Cox regression models. We included 107 Stage III UC patients treated with NAIC (n = 83) or cICI (n = 24). NAIC was discontinued in 11 patients due to progression (n = 6; 7%) or toxicity (n = 5; 6%), while cICI was discontinued in 6 patients (25%) after 2 cycles due to toxicity (P =.205). After NAIC, patients had surgical resection (n = 50; 60%), chemoradiation (n = 26; 30%), or no consolidating treatment due to progression (n = 5; 6%) or toxicity (n = 2; 2%). After cICI, all patients underwent resection. After resection (n = 74), complete pathological response (ypT0N0) was achieved in 11 (22%) NAIC-patients and 11 (46%) cICI-patients (P =.056). Median (IQR) follow-up was 26 (20-32) months. cICI was associated with superior progression-free survival (P =.003) and overall survival (P =.003) compared to NAIC. Our study showed superior survival in Stage III UC patients pretreated with cICI if compared to NAIC. Our findings provide a strong rationale for validation of cICI for locally advanced UC in a comparative phase-3 trial.
AB - Despite treatment with cisplatin-based chemotherapy and surgical resection, clinical outcomes of patients with locally advanced urothelial carcinoma (UC) remain poor. We compared neoadjuvant/induction platinum-based combination chemotherapy (NAIC) with combination immune checkpoint inhibition (cICI). We identified 602 patients who attended our outpatient bladder cancer clinic in 2018 to 2019. Patients were included if they received NAIC or cICI for cT3-4aN0M0 or cT1-4aN1-3M0 UC. NAIC consisted of cisplatin-based chemotherapy or gemcitabine-carboplatin in case of cisplatin-ineligibility. A subset of patients (cisplatin-ineligibility or refusal of NAIC) received ipilimumab plus nivolumab in the NABUCCO-trial (NCT03387761). Treatments were compared using the log-rank test and propensity score-weighted Cox regression models. We included 107 Stage III UC patients treated with NAIC (n = 83) or cICI (n = 24). NAIC was discontinued in 11 patients due to progression (n = 6; 7%) or toxicity (n = 5; 6%), while cICI was discontinued in 6 patients (25%) after 2 cycles due to toxicity (P =.205). After NAIC, patients had surgical resection (n = 50; 60%), chemoradiation (n = 26; 30%), or no consolidating treatment due to progression (n = 5; 6%) or toxicity (n = 2; 2%). After cICI, all patients underwent resection. After resection (n = 74), complete pathological response (ypT0N0) was achieved in 11 (22%) NAIC-patients and 11 (46%) cICI-patients (P =.056). Median (IQR) follow-up was 26 (20-32) months. cICI was associated with superior progression-free survival (P =.003) and overall survival (P =.003) compared to NAIC. Our study showed superior survival in Stage III UC patients pretreated with cICI if compared to NAIC. Our findings provide a strong rationale for validation of cICI for locally advanced UC in a comparative phase-3 trial.
KW - checkpoint inhibition
KW - chemotherapy
KW - immune
KW - neoadjuvant
KW - urothelial cancer
UR - http://www.scopus.com/inward/record.url?scp=85131540407&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ijc.34125
DO - https://doi.org/10.1002/ijc.34125
M3 - Article
C2 - 35603905
SN - 0020-7136
VL - 151
SP - 2004
EP - 2011
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 11
ER -