KEY TAKEAWAYS
- The CUPem phase II trial aimed to assess the feasibility of pembro treatment post-failure of at least one therapy line in a prospective phase 2 trial.
- Pembro showed promise in CUP with lasting disease control for some beyond 2nd line, warranting further study to identify who benefits most.
Cancer of unknown primary (CUP) poses a prevalent challenge, diagnosed through the sequential exclusion of known origins. Median survival, except in rare favorable subsets, is dismal at under 10 months with first-line platinum-based cytotoxics. Less than 10% are eligible for therapies targeting actionable mutations, and fewer than 20% qualify for second-line treatments.
Limited studies exist beyond first-line therapy, needing a standard of care (SOC). CUP may exhibit distinctive biology related to immune system evasion, contributing to early metastatic spread.
Dr. Harpreet Wasan and his team conducted a study that aimed to assess the viability of pembro treatment following the failure of at least one line of therapy in a prospective phase 2 trial.
The study aimed to enroll at least 57 CUP patients progressing after one line of chemotherapy, with RECIST measurable disease, across three UK centers. Pembro (200 mg IV Q21d) was administered until disease progression or intolerance. Due to significant COVID-related recruitment disruption in this rare population, the study design was revised to a minimum of 31 patients after an interim pre-planned futility analysis at 24 patients, ensuring 0.80 power to detect a 2-month progression-free survival (PFS) improvement
Of 35 consenting patients, 30 were assessable (Database lock Aug 2023). Median age was 60 (range 33–77), 67% female, ECOG 0-1 vs 2: 83/17%. Prior treatment included 63% with 1 line of chemotherapy, 27% with 2 lines, 10% with 3 or more lines, and 10% with prior radiotherapy. Median PFS (first RECIST PD) was 4.0 months (95% CI 3.2-7.5), and median OS was 11.5 months (95% CI 6.5-NR). At 6/12/18/24 & 36 months, the percentages of patients not progressing on trial treatment were 33/23/17/13/13%, respectively.
Two patients who had not progressed discontinued treatment due to related adverse events (AEs), one maintaining stable disease for >36 months, including 9 months post-discontinuation. Pembro was well-tolerated with no unexpected AEs.
The results demonstrated that further exploring pembro in CUP is warranted, given its promising activity and sustained disease control in a notable subset of patients beyond the second line, with overall survival comparable to first-line CUP studies. Ongoing clinical-translational research holds the potential for identifying predictive biomarkers. Research was sponsored by Imperial College London.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT03752333
Wasan HS et al. (2023) ‘’Outcomes of CUPem: A prospective Phase II multicentre clinical Trial of Pembrolizumab in patients with pre-treated Cancer of Unknown Primary.’’ Presented at ESMO I-O 2023 (110P).
