BASELINE CHARACTERISTICS | OPDIVO (n=353) |
PLACEBO (n=356) |
---|---|---|
Median age (range), years | 65.3 (30–92) | 65.9 (42–88) |
Male, % | 75.1 | 77.2 |
Region, % United States |
13.9 |
14.9 |
ECOG PS,* % 0 |
63.5 |
62.1 |
Tumor origin at initial diagnosis, % Urinary bladder |
|
|
Minor histological variants present, % | 41.1 | 39.6 |
PD-L1 ≥1% (IVRS), % | 39.7 | 39.9 |
Prior neoadjuvant cisplatin, % | 43.3 | 43.5 |
Pathologic T stage at resection,‡§ % pTO–2 |
22.7 58.4 16.1 2.5 |
24.2 57.3 17.4 0.8 |
Nodal status at resection,§ % N+ |
47.3 |
47.2 |
OPDIVO Qvantig™ (nivolumab + hyaluronidase-nvhy) is now approved as a subcutaneous injection
Adjuvant Treatment of UC
A chance to change the future for patients with high-risk UC1-4
In the adjuvant treatment of adult patients with UC at high risk of recurrence after radical resection of UC
PD-L1=programmed death-ligand 1; UC=urothelial carcinoma.
INDICATION OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
Scroll down for the latest overall survival data
There is a need for approved adjuvant options to help extend DFS
In a retrospective, observational cohort study* of patients 65 years and older with UC at high risk† of recurrence after radical resection, the mDFS‡ was 13.5 months.5§
Patients who received neoadjuvant chemotherapy were also included.5
*This study included 665 patients from the SEER-Medicare database who had UC of the bladder or upper tract at a high risk of recurrence after radical resection.5
†Prior neoadjuvant chemotherapy: AJCC stage T2–T4a or N+ and M0 for bladder site and AJCC stage T2–T4 or N+ and M0 for other sites; no neoadjuvant chemotherapy: AJCC stage T3–T4a or N+ and M0 for bladder site and AJCC stage T3–T4 or N+ and M0 for other sites.5
‡DFS was defined as the first occurrence of surgery, radiotherapy, ≥1 administration of systemic chemotherapy, or palliative TURBT after 120 days of primary surgical resection. Those who received adjuvant treatment within 120 days of radical resection were excluded from the study.5
§mDFS was 13.5 months (95% CI: 11.3–16.8).5
AJCC=American Joint Committee on Cancer; CI=confidence interval; DFS=disease-free survival; mDFS=median disease-free survival; SEER=Surveillance, Epidemiology, and End Results Program; TURBT=transurethral resection of bladder tumor.
Scroll down to learn more about Checkmate 274
CHECKMATE 274: FOR ADULT PATIENTS WITH UC AT HIGH RISK OF RECURRENCE AFTER RADICAL RESECTION OF UC
First and only phase 3, placebo-controlled adjuvant trial in patients with UC1,2,6
Checkmate 274 includes data from an extended follow-up analysis at a minimum follow-up time of 31.6 months.7¶
- This trial excluded patients with any condition requiring systemic treatment with immunosuppressants (eg, glucocorticoids) within 2 weeks of treatment8
- DFS was defined as time to first recurrence (local urothelial tract, local non-urothelial tract, or distant metastasis), or death1
- Minimum follow-up time in all randomized patients was 5.9 months. Median follow-up time in all randomized patients was 20.9 months for OPDIVO® (nivolumab) and 19.5 months for placebo2
*Urothelial carcinoma originating in the bladder or upper urinary tract (renal pelvis or ureter).1
†AJCC tumor stage.9
‡Using the PD-L1 IHC 28-8 pharmDx assay.1
§Approved dosing for OPDIVO is 240 mg IV q2w or 480 mg IV q4w.1
||OS data are immature at the time of the planned interim analysis.1,2
¶Based on extended follow-up analysis in all randomized patients at a minimum follow-up time of 31.6 months and a median follow-up time of 37.4 months for OPDIVO and 33.9 months for placebo.7
ECOG PS=Eastern Cooperative Oncology Group Performance Status; ICH=immunohistochemistry; IV=intravenous; OS=overall survival; q2w=every 2 weeks; q4w=every 4 weeks.
Select Important Safety Information
Serious Adverse Reactions
In Checkmate 274, serious adverse reactions occurred in 30% of patients receiving OPDIVO (n=351). The most frequent serious adverse reaction reported in ≥2% of patients receiving OPDIVO was urinary tract infection. Fatal adverse reactions occurred in 1% of patients; these included events of pneumonitis (0.6%).
Common Adverse Reactions
In Checkmate 274, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=351) were rash (36%), fatigue (36%), diarrhea (30%), pruritus (30%), musculoskeletal pain (28%), and urinary tract infection (22%).
Please see additional Important Safety Information below and U.S. Full Prescribing Information for OPDIVO.
Patient eligibility criteria
CHECKMATE 274 DEFINED PATIENTS AT HIGH RISK OF RECURRENCE
ACCORDING TO THE FOLLOWING CRITERIA1:
OPDIVO is the only FDA-approved adjuvant option for these patients, regardless of prior neoadjuvant chemotherapy, nodal involvement, or PD-L1 status1
*Cisplatin-based.1
†Are not eligible for or refused cisplatin-based chemotherapy.1
Checkmate 274 baseline characteristics6
In the OPDIVO arm:
- ~40% of patients expressed PD-L1 ≥1%6
- ~43% of patients received prior neoadjuvant chemotherapy6
- ~47% of patients had nodal involvement6
*Not reported for 1 patient in the placebo arm.6
†ECOG PS of 2 was permitted only for patients who did not receive cisplatin-based neoadjuvant chemotherapy and were ineligible for adjuvant cisplatin-based chemotherapy.6
‡The AJCC tumor staging included patients with N+, N0, or Nx.6,9
§Not reported for 1 patient in each arm.6
IVRS=Interactive Voice-Response System.
Continued disease-free survival with OPDIVO at 31.6-month minimum follow-up7*†
DISEASE-FREE SURVIVAL IN ALL RANDOMIZED PATIENTS
(31.6-MONTH MINIMUM FOLLOW-UP)7
Limitation: Checkmate 274 was not powered to detect differences in the treatment effect at extended follow-up analysis; therefore, results from this exploratory analysis should be interpreted with caution.
Primary analysis:
mDFS in all randomized patients (minimum follow-up time of 5.9 months; median follow-up time of 20.9 months for OPDIVO and 19.5 months for placebo)1,2
- OPDIVO: 20.8 months (95% CI: 16.5–27.6)1,2
- Placebo: 10.8 months (95% CI: 8.3–13.9)1,2
- HR=0.70 (95% CI: 0.57–0.86); P=0.00081,2
mDFS in patients with PD-L1 ≥1% (minimum follow-up time of 6.3 months; median follow-up time of 22.1 months for OPDIVO and 18.7 months for placebo)1,10
- OPDIVO: NR (95% CI: 21.2–NE)1
- Placebo: 8.4 months (95% CI: 5.6–21.2)1
- HR=0.55 (95% CI: 0.39–0.77); P=0.00051
Extended follow-up analysis:
mDFS in patients with PD-L1 ≥1% (median follow-up time of 39.8 months for OPDIVO and 33.3 months for placebo)7
- OPDIVO: 52.6 months (95% CI: 25.8–NE)7
- Placebo: 8.4 months (95% CI: 5.6–17.9)7
- HR=0.52 (95% CI: 0.37–0.72)7
Primary analysis exploratory and secondary endpoint information
- In exploratory subgroup analyses in patients with upper tract UC (n=149), no improvement in DFS was observed in the nivolumab arm compared to the placebo arm. The unstratified DFS hazard ratio estimate was 1.15 (95% CI: 0.74–1.80)1
- In an exploratory subgroup analysis in patients with PD-L1 expression of <1% (n=414), the unstratified DFS hazard ratio estimate was 0.83 (95% CI: 0.64–1.08)1
- OS data are immature with 33% of deaths in the overall randomized population. In the UTUC subpopulation, 37 deaths occurred (20 in the nivolumab arm, 17 in the placebo arm)1
*Based on extended follow-up analysis in all randomized patients at a minimum follow-up time of 31.6 months and a median follow-up time of 37.4 months for OPDIVO and 33.9 months for placebo.7
†Vs placebo.7
HR=hazard ratio; NE=not estimable; NR=not reached; UTUC=upper tract urothelial carcinoma.
Overall survival with OPDIVO11*
OVERALL SURVIVAL IN ALL RANDOMIZED PATIENTS
(INTERIM ANALYSIS AT 31.6-MONTH MINIMUM FOLLOW-UP; 36.1-MONTH MEDIAN FOLLOW-UP)11
Limitation: OS data are immature and follow-up is ongoing as the prespecified statistical boundary for significance was not met at the time of this analysis. Results are descriptive and should be interpreted with caution.
Primary analysis secondary endpoint information (minimum follow-up time of 5.9 months; median follow-up time of 20.9 months for OPDIVO and 19.5 months for placebo)2
- OS data are immature with 33% of deaths in overall randomized population. In the UTUC subpopulation, 37 deaths occurred (20 in the nivolumab arm, 17 in the placebo arm)1
Median OS in patients with PD-L1 ≥1% (interim analysis at minimum follow-up time of 11.4 months; median follow-up time of 23.4 months)11
- OPDIVO (n=140): NR (95% CI: NE)11
- Placebo (n=142): NR (95% CI: 29.0–NE)11
- HR=0.56 (95% CI: 0.36–0.86)11
*Based on pre-planned interim analysis in all randomized patients at a minimum follow-up time of 31.6 months and a median follow-up time of 36.1 months.11
OPDIVO dosing options1,2
- OPDIVO is administered as an IV infusion over 30 minutes1
- Based on exploratory dose exposure-response relationships for efficacy and safety, OPDIVO 240 mg q2w and 480 mg q4w are predicted to be similar12
- Review the Full Prescribing Information for OPDIVO prior to initiation, including recommended dosage and dose modifications
- No premedication required1
Safety Data
View a selected safety profile of adverse reactions seen in clinical trials.
Dosing Schedules
Find dosing information to get patients started on therapy.
More UC Indications
Learn about another urothelial carcinoma indication.
Learn more about how OPDIVO is approved for use in earlier stages of cancer
- References:OPDIVO [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
- Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021;384(22):2102-2114.
- Jodon G, Fischer SM, Kessler ER. Treatment of urothelial cancer in elderly patients: focus on immune checkpoint inhibitors. Drugs Aging. 2018;35(5):409-421.
- Duplisea JJ, Dinney CPN. Should chemotherapy still be used to treat all muscle invasive bladder cancer in the "era of immunotherapy"? Expert Rev Anticancer Ther. 2019;19(7):543-545.
- Drakaki A, Pantuck A, Mhatre SK, et al. "Real-world" outcomes and prognostic indicators among patients with high-risk muscle-invasive urothelial carcinoma. Urol Oncol. 2021;39(1):76.e15-76.e22.
- Bajorin DF, Witjes JA, Gschwend JE, et al. First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab versus placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma. Oral presentation at ASCO GU 2021. Abstract 391.
- Galsky MD, Witjes JA, Gschwend JE, et al. Extended follow-up results from the CheckMate 274 trial. Oral presentation at ASCO 2023. Abstract LBA443.
- Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021;384(22):2102-2114 [supplementary appendix].
- Bladder cancer early detection, diagnosis, and staging. American Cancer Society. Accessed July 7, 2022. https://www.cancer.org/content/dam/CRC/PDF/Public/8559.00.pdf
- Data on file. NIVO 639. Princeton, NJ: Bristol-Myers Squibb Company; 2021.
- Galsky MD, Witjes JA, Gschwend JE, et al. Extended follow-up from CheckMate 274 including the first report of overall survival outcomes. Oral presentation at EAU 2024.
- Long GV, Tykodi SS, Schneider JG, et al. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018;29(11):2208-2213.