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ASCO 2024

ASCO 2024: Characterization of Complete Responders to Nivolumab + Gemcitabine-Cisplatin vs Gemcitabine-Cisplatin Alone and Patients with Lymph Node–only Metastatic Urothelial Carcinoma from the CheckMate 901 Trial

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between May 31 and June 4 was host to the Oral Abstract Session: Genitourinary Cancer-Kidney and Bladder. Dr. Matt Galsky presented a post hoc analysis of complete responders to nivolumab + gemcitabine-cisplatin vs gemcitabine-cisplatin alone and patients with lymph node-only metastatic urothelial carcinoma from the CheckMate 901 trial.


For decades, cisplatin-based chemotherapy has stood as the standard of care for eligible patients with unresectable or metastatic urothelial carcinoma (mUC), yielding robust response rates but not sustained responses.1

The CheckMate 901 (NCT03036098) is a phase 3, multinational, open-label trial that randomly assigned patients with previously untreated, unresectable or mUC to intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin every 3 weeks for up to six cycles, followed by nivolumab maintenance (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone (the standard of care at the time) every 3 weeks for up to six cycles. The study design is illustrated below:

The combination of Nivolumab + gemcitabine-cisplatin (GC) demonstrated:

  • Significant improvement in overall survival (OS) (HR 0.78; 95% CI, 0.63 to 0.96; p=0.02)
  • Progression-free survival (PFS) (HR 0.72; 95% CI, 0.59 to 0.88; P = 0.001)
  • Overall response rate (ORR) 57.6% with Nivolumab+GC vs 43.1% with GC alone
  • Complete responses (CR) 21.7% with Nivolumab+GC vs 11.8% with GC alone 

Having lymph node-only metastatic disease is a favorable prognostic factor in patients with mUC, and a subset of patients achieve durable disease-free, treatment-free survival with GC +/- surgical consolidation. Dr. Galsky presented a post hoc analysis of CheckMate 901 characterizing the subset of patients who were complete responders, with further analysis of patients with lymph node-only metastatic disease.

A total of 102/608 (16.8%) of patients achieved a complete response (CR) in the CheckMate 901 study. Among these, 34 (51.5%) in the Nivolumab+GC arm and 19 (52.8%) in the GC alone arm had lymph node-only mUC, as shown below:
The investigators conducted an exploratory analysis of patients with lymph node-only disease, given that over 50% of these patients achieved complete responses in both treatment arms. The table below shows the baseline characteristics of patients with lymph node-only mUC in both treatment arms of CheckMate 901.
Among all randomized patients, 54 treated with Nivolumab+GC and 56 treated with GC had lymph node-only mUC. In this subgroup, the ORR and CR rate were 81.5% (95% CI 68.6-90.7) and 63.0% for Nivolumab+GC, respectively, compared to 64.3% (95% CI 50.4-76.6%) and 33.9% for GC alone, respectively.Among all randomized patients, 54 treated with Nivolumab+GC and 56 treated with GC had lymph node-only mUC. In this subgroup, the ORR and CR rate were 81.5% (95% CI 68.6-90.7) and 63.0% for Nivolumab+GC, respectively, compared to 64.3% (95% CI 50.4-76.6%) and 33.9% for GC alone
The ORR for patients with LN-only mUC, categorized by the site of lymph node involvement, is depicted in the figure below. Briefly, patients with pelvic lymph nodes had a 79% ORR and a CR of 62%, while patients with retroperitoneal lymph nodes had a 77% ORR and a 63% CR.ORR for patients with LN-only mUC, categorized by the site of lymph node involvement, is depicted in the figure below. Briefly, patients with pelvic lymph nodes had a 79% ORR and a CR of 62%, while patients with retroperitoneal lymph nodes had a 77% ORR and a 63% CR
The Swimmers plot below illustrates the treatment-free intervals of patients with lymph node-only mUC achieving a CR in CheckMate 901. In the Nivolumab+GC arm, 41% experienced a treatment-free interval compared to only 16% in the GC arm. Swimmers plot below illustrates the treatment-free intervals of patients with lymph node-only mUC achieving a CR in CheckMate 901. In the Nivolumab+GC arm, 41% experienced a treatment-free interval compared to only 16% in the GC arm
In lymph node-only mUC patients with CR, the median time to CR was 2 months in both treatment groups. However, the median duration of CR was not reached (NR) in the Nivolumab+GC arm compared to 8.7 months in the GC arm. At 12 months, the CR rate was more than double for Nivolumab+GC vs GC (70% vs 32%), reinforcing that the addition of Nivolumab improves the duration of response in this subset of patients.median duration of CR was not reached (NR) in the Nivolumab+GC arm compared to 8.7 months in the GC arm. At 12 months, the CR rate was more than double for Nivolumab+GC vs GC (70% vs 32%)
The median OS in patients with lymph node-only mUC was 46.3 (95% CI 24.0-NR) months with Nivolumab+GC versus 24.9 (95% CI 21.4-29.9) months with GC (HR 0.58, 95% CI 0.34-1.00).
The median OS in patients with lymph node-only mUC was 46.3 (95% CI 24.0-NR) months with Nivolumab+GC versus 24.9 (95% CI 21.4-29.9) months with GC (HR 0.58, 95% CI 0.34-1.00)
The median PFS in patients with lymph node-only mUC was 30.5 (95% CI 9.6-NR) months with Nivolumab+GC versus 8.8 (95% CI 7.5-10.9) months with GC (HR 0.38, 95% CI 0.22-0.66) as illustrated in the graphic below.The median PFS in patients with lymph node-only mUC was 30.5 (95% CI 9.6-NR) months with Nivolumab+GC versus 8.8 (95% CI 7.5-10.9) months with GC (HR 0.38, 95% CI 0.22-0.66) as illustrated in the graphic below
Dr. Galsky concluded his presentation by delivering the following key messages:

  • The post hoc analysis of CheckMate 901 revealed that among patients achieving complete response (CR), more than half had lymph node-only mUC.
  • In patients with lymph node-only metastatic urothelial carcinoma (mUC), Nivolumab+GC demonstrated durable disease control and clinically meaningful improvements in OS and PFS compared to patients who received GC alone.
  • Lymph node-only mUC represents a distinct clinical entity, and with Nivolumab+GC, we may alter the trajectory of this disease through consolidation therapy, especially for patients with pelvic metastatic lymph nodes.
  • These findings strengthen the rationale for Nivolumab plus cisplatin-based chemotherapy as a standard first-line treatment option for patients with mUC.

Presented by: Matt D. Galsky, MD, FASCO, Director of Genitourinary Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY

Written by: Julian Chavarriaga, MD – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @chavarriagaj on Twitter during the 2024 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between May 31st and June 4th.

References

  1. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017;376(11):1015-1026. doi:10.1056/NEJMoa1613683
  2. van der Heijden MS, Sonpavde G, Powles T, Necchi A, Burotto M, Schenker M, Sade JP, Bamias A, Beuzeboc P, Bedke J, Oldenburg J, Chatta G, Ürün Y, Ye D, He Z, Valderrama BP, Ku JH, Tomita Y, Filian J, Wang L, Purcea D, Patel MY, Nasroulah F, Galsky MD; CheckMate 901 Trial Investigators. Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. N Engl J Med. 2023 Nov 9;389(19):1778-1789. doi: 10.1056/NEJMoa2309863. Epub 2023 Oct 22. PMID: 37870949.