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LBA16 – Primary analysis of efficacy and safety in the CUPISCO trial: A randomised, global study of targeted therapy or cancer immunotherapy guided by comprehensive genomic profiling (CGP) vs platinum-based chemotherapy (CTX) in newly diagnosed, unfavourable cancer of unknown primary (CUP)
Background
With platinum-based CTX, prognosis of patients (pts) with unfavourable CUP is poor; however, CGP may inform treatment strategies based on cancer genomics. The CUPISCO trial (NCT03498521) compared the efficacy and safety of molecularly guided therapy (MGT) vs standard platinum-based CTX in pts with newly diagnosed, unfavourable, non-squamous CUP.
Methods
Pts had central eligibility review-confirmed CUP with ≥1 measurable lesion (investigator-assessed via RECIST v1.1). All had tumour tissue and/or blood CGP (Foundation Medicine, Inc.). After 3 induction CTX cycles, pts with disease control were randomised 3:1 to MGT (investigator’s choice from 12 regimens after molecular tumour board advice) or continuation with ≥3 more CTX cycles (category 1; shown here), stratified by gender and response to induction CTX. Pts with progressive disease received MGT (category 2). The primary endpoint was progression-free survival (PFS) in category 1 pts. Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DoR) and disease control rate (DCR). Safety was also assessed. Exploratory endpoints included quality of life (QoL).
Results
From Jul 2018–Dec 2022, 436 category 1 pts were randomised: 326 to MGT; 110 to CTX. Median PFS (intent-to-treat population) was 6.1 months (95% confidence interval [CI] 4.7–6.5) with MGT vs 4.4 months (4.1–5.6) with CTX (hazard ratio [HR] 0.72; 95% CI 0.56–0.92; P=0.0079). Median OS was 14.7 (95% CI 13.3–17.3) vs 11.0 months (9.7–15.4), respectively (HR 0.82; 95% CI 0.62–1.09; P=0.1779), though OS data were immature at cutoff. ΔORR was 9.6% (95% CI 2.4–16.8, P=0.0141) in favour of MGT, with similar DoR in each arm (HR 0.95; 95% CI 0.33–2.72). ΔDCR was 4.7% (95% CI –6.4–15.9; P=0.3922) in favour of MGT. Adverse event rates were generally similar with MGT vs CTX; no difference in QoL was observed.
Conclusions
In pts with newly diagnosed, unfavourable, non-squamous CUP who responded to induction CTX, CGP with MGT improved PFS. Early CGP and MGT should be considered the new standard of care for these pts.