Treatment option

Clinical baseline characteristics

Combination chemotherapy (cisplatin-based chemotherapy/gemcitabine + carboplatin)

· For cisplatin-based chemotherapy, the patient has to have:

o A good ECOG performance status

o Good renal function (creatinine clearance: >60 mL/minute)

o Good cardiac function

· For carboplatin-based chemotherapy, the experts often give it to patients with poor performance status, renal failure so as to adjust according to GFR as well as those with compromised cardiac function.

· Other factors to consider are age, hematologic and hepatic functions, neuropathy, and hearing status.

Pembrolizumab

· ECOG performance status

· Unfit patient

· Renal function impairment

· Cardiac failure

· MSI-H tumors

· PD-L1 positivity in first line

· Platinum ineligibility

· Autoimmune conditions

· In all patients in second line if not used in first line for advanced setting or after failure of first-line platinum-based chemotherapy

· In the first-line setting in patients who are cisplatin-ineligible

Atezolizumab

· ECOG performance status

· Unfit patient

· Renal function impairment

· Cardiac failure

· PD-L1 status in first line

· PD-L1 positivity in first line

· Platinum ineligibility

· Autoimmune conditions

· In all patients in second line if not used in first line for advanced setting

· In the first-line setting in patients who are cisplatin-ineligible

Nivolumab

· ECOG performance status

· Platinum ineligibility

· Autoimmune conditions

· In the adjuvant patient in patients who received or not neoadjuvant chemotherapy; all comers can benefit from this treatment

· In the second-line setting after failure of first-line chemotherapy regimen whether cisplatin or carboplatin

Not recommended as first-line option but in subsequent lines in case of resistance to platinum.

One expert reported not using nivolumab for the treatment of locally advanced/metastatic UC patients.

The FGFR inhibitor erdafitinib

· In second- or third-line patients harboring FGFR2 and 3 genetic alterations

· Creatinine clearance

· Resistance to first-line platinum with NGS that showed expression of FGFR or amplification

Avelumab in maintenance

· In patients who received chemotherapy platinum-based chemotherapy for advanced setting provided they have no underlying autoimmune disease that precludes the use of immune checkpoint inhibitors

· Objective response or stable disease following first-line platinum-based therapy

· Response to the Javelin 100 chemotherapy scheme

· Autoimmune conditions

· Platinum ineligibility