Keynote-992 (blaas, 2de lijn)

De Keynote-992 (KN-922) is een wereldwijde studie naar het effect van immunotherapie met pembrolizumab met chemoradiatie. Chemoradiatie is bestraling gecombineerd met chemotherapie die het effect van de bestraling verbetert. Chemoradiatie wordt ook in Nederland al vele jaren als curatieve blaassparende behandeling bij spierinvasieve blaaskanker toegepast. De gebruikte chemotherapie is in lagere dosering dan hetgeen gebruikt wordt om kankercellen zelf te vernietigen. De meeste patiënten hebben van deze zogenaamde sensitizing dosis geen enkele  last. Er is daarbij evenmin sprake van haarverlies of misselijkheid. De 5 jaars ziektevrije uitkomsten zijn met de steeds verder verbeterende bestralingstechnieken min of meer gelijk aan een radicale blaasverwijdering. KN-992 betreft een vergelijkend onderzoek; de helft van de patiënten krijgt de standaardbehandeling; chemoradiatie, de andere helft chemoradiatie plus pembrolizumab. Lees hier meer over chemoradiatie.

In Nederland participeren het AvL en het ErasmusMC in deze studie.

Inclusiecriteria

  1. Has a histologically confirmed diagnosis of MIBC with predominant urothelial histology (histology and presence of muscle invasion to be confirmed by BICR) obtained via a diagnostic or maximal TURBT performed within 60 days prior to enrollment (signing of ICF). Note: Participants with mixed histology are eligible provided the urothelial component is ≥50%.
  2. Has clinically non-metastatic bladder cancer (N0M0) determined by imaging (CT of the chest and CTU/MRU of abdomen and pelvis), confirmed by BICR.
  3. Has provided tumor specimen to the central vendor to determine PD-L1 status prior to Randomization
  4. PS 0,1 OR 2, and adequate organ function

Exclusie criteria

  1. Has the presence of diffuse CIS (multiple foci of CIS) throughout the bladder.
  2. Has the presence of UC at any site outside of the urinary bladder in the previous 2 years except for Ta/T1/CIS of the upper tract if the patient has undergone a complete nephroureterectomy.
  3. Has the presence of any small cell or neuroendocrine component in the tumor tissue sample.
  4. Has a known additional malignancy that is progressing or has required active therapy within the past 3 years. Participants with low-risk prostate cancer (T1-T2a, Gleason score ≤6, and PSA <10 ng/mL) either treated with definitive intent any time prior to Screening or untreated in active surveillance are not excluded.
  5. Has the presence of bilateral hydronephrosis during the Screening period. Note: Participants with unilateral hydronephrosis are eligible if their measured or calculated GFR per the institutional standard permits enrollment on the study (per Inclusion Criterion #6).
  6. Has limited bladder function with frequency of small amounts of urine (< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  7. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  8. Has an active infection requiring systemic therapy.
  9. Has a known history of HIV infection of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative]
  10. Has a history or current evidence of any condition that might confound the results of the study, in the opinion of the treating investigator.