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.

Clinical trial identification

NCT03498521 / 13 April 2018.

Editorial acknowledgement

Research support for third-party writing assistance for this abstract, furnished by Daniel Clyde, PhD, and Katie Wilson, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

L. Mileshkin: Financial Interests, Institutional, Invited Speaker, Institutional funding from BeiGene for an investigator-initiated trial: BeiGene; Non-Financial Interests, Other, Co-chair of the Steering Committee for the CUPISCO trial in CUP (non-remunerated): Roche; Non-Financial Interests, Member, Member of multiple other cancer organisations as above: ASCO, MOGA, COSA, IGCS, GCIG. T. Bochtler: Financial Interests, Institutional, Expert Testimony, I work as study oncologist for the CUPISCO trial, which is sponsored by Roche. The work includes work as clinician in the molecular tumor board (MTB), advising for eligibility decisions with respect to CUP diagnosis, and workshops with respect to the CUPISCO trial. I have received reimbursement for study related travels and I have received remuneration for my work as study oncologist for the benefit of my employer. I have not taken any money personally.: Roche. C. Pauli: Financial Interests, Institutional, Invited Speaker, Presentations and lectures about molecular profiling.: Roche; Financial Interests, Institutional, Invited Speaker, Funding support for a research project.: Roche. G. Durán-Pacheco: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. C. Arslan: Financial Interests, Personal and Institutional, Other, Speaker honoAdvisory board, Research grant, honoraria: Bristol Myers Squibb; Financial Interests, Institutional, Other, Additional costs linked to the study: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Investigator fees: F. Hoffmann-La Roche Ltd; Financial Interests, Personal and Institutional, Advisory Board: Janssen; Financial Interests, Personal and Institutional, Research Grant: Sanofi, Lilly, Yuhan, Henlius; Financial Interests, Personal, Other, Advisory board, honoraria: Astellas; Financial Interests, Personal and Institutional, Other, Advisory board, Research grant, honoraria: Novartis, AstraZeneca, Bristol Myers Squibb, Pfizer, MSD; Financial Interests, Personal and Institutional, Other, Advisory board, Research grant, honoraria, travel support: Amgen; Financial Interests, Personal, Other, Honoraria: Astellas; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. F. Bigot: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.; Financial Interests, Institutional, Other, Additional costs linked to the study: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Investigator fees: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, BMS; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD, BMS; Financial Interests, Personal, Other, Travel support/accommodation: Takeda, MSD. N. Chalabi: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.. N. Cook: Financial Interests, Institutional, Invited Speaker: Roche, Taiho, Roche, AstraZeneca, RedX, Orion, Avacta, Bayer, Eisai, UCB, Starpharma, Boehringer, Stemline, Ergomed; Non-Financial Interests, Advisory Role: Roche. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Invited Speaker: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. F. Losa: Financial Interests, Institutional, Other, Additional costs linked to the study: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Investigator fees: F. Hoffmann-La Roche Ltd.; Financial Interests, Institutional, Research Grant, Institutional research funding: F. Hoffmann-La Roche Ltd., Amgen, Merck; Financial Interests, Personal, Other, Travel/accommodation expenses: F. Hoffmann-La Roche Ltd., Merck; Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche Ltd., Amgen, Merck, Sanofi, Servier; Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche Ltd., Sanofi; Financial Interests, Personal, Expert Testimony: F. Hoffmann-La Roche Ltd., Sanofi; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.. J. Menezes: Financial Interests, Institutional, Other, Additional costs linked to the study: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Investigator fees: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party editing assistance from F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd.. C. Michaud: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party editing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. M. Ozguroglu: Financial Interests, Personal, Advisory Board: Janssen, Sanofi, Astellas; Financial Interests, Institutional, Other, Additional costs linked to the study: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Investigator fees: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Honoraria: Novartis, F. Hoffmann-La Roche Ltd., Janssen, Sanofi, Astellas; Financial Interests, Personal, Other, Travel support: BMS, Janssen, AstraZeneca; Financial Interests, Personal, Other, Speaker Support: AstraZeneca; Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. R.A. Pazo Cid: Financial Interests, Personal, Advisory Board: Roche, BMS, Servier, Ipsen; Financial Interests, Personal, Invited Speaker: Servier, BMS, Roche, Eisai; Financial Interests, Personal, Expert Testimony: Lilly, Astra-Zeneca; Financial Interests, Personal and Institutional, Invited Speaker, Support for manuscript presentation (funding, provision of study materials, medical writing, article processing charges): Ipsen, Astellas. J.S. Ross: Financial Interests, Personal, Full or part-time Employment, Medical Director: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche Holdings, Tango Therapeutics, Celsius Therapeutics. K. Shiu: Financial Interests, Personal, Invited Speaker, Educational Webinars on CRC and UGI cancer management with immunotherapy: BMS; Financial Interests, Personal, Advisory Board, Advisory Board on Regorafenib for chemorefractory mCRC in readiness for NICE application: Bayer; Financial Interests, Personal, Invited Speaker, Educational webinars on Pembrolizumab for MSI-High CRC, as well as OG cancers: MSD; Financial Interests, Personal, Advisory Board, For Pembrolizumab in CRC of OG cancers pre or NICE application or post NICE approval: MSD; Financial Interests, Personal, Invited Speaker, Webinars on updates on management of mCRC: Merck Serono; Financial Interests, Personal, Advisory Board, On Mirati GI Global Advisory Board: Mirati Therapeutics; Financial Interests, Personal, Invited Speaker, To update company on indications/updates in landscape of immunotherapy and vaccines in GI cancers: Nouscom; Financial Interests, Personal, Advisory Board, Advisory on Cancer of Unknown Primary, new indications of molecular profiling usingFoundation Medicine 1: Roche; Financial Interests, Personal, Advisory Board, Advisory Board on Lonsurf for chemorefractory mCRC in readiness for NICE application: Servier; Financial Interests, Institutional, Invited Speaker, For MATTERHORN Trial: AstraZeneca; Financial Interests, Institutional, Invited Speaker, UK Chief Investigator on KEYNOTE 177, KEYNOTE 859, KEYNOTE 811, LEAP 17, MK1308A-008 trials: MSD; Financial Interests, Institutional, Research Grant, Chief Investigator of investigator initiated, MSD funded NEOPRISM-CRC trial: MSD; Financial Interests, Institutional, Invited Speaker, UCLH PI for LEAP 15 and MK4280A-007 trials: MSD; Financial Interests, Institutional, Invited Speaker, UK Chief Investigator for NOUS209-001 trial: Nouscom; Financial Interests, Institutional, Invited Speaker, UK Chief Investigator for CUPSICO trial: Roche; Financial Interests, Personal, Invited Speaker, Steering Committee Member of CUPISCO trial: Roche; Non-Financial Interests, Member: ASCO, Association of Cancer Physicians UK. M. Stahl: Financial Interests, Personal, Invited Speaker: Amgen, Lilly Deutschland, Pfizer, Roche, Ipsen, Servier; Financial Interests, Personal, Advisory Board: Bristol, Myers Squibb, Daiichy-Sankyo, Merck, Sharp & Dohme, Novartis. M. Thomas: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Funding, Research funding: Support for third-party editing assistance from F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd.. H. Moch: Financial Interests, Personal, Invited Speaker: Roche Ag, Amgen; Financial Interests, Personal, Advisory Board: Merck, AstraZeneca, Janssen; Financial Interests, Institutional, Research Grant: Roche. A. Krämer: Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche Ltd., Daiichi Sankyo, AbbVie; Financial Interests, Institutional, Other, Additional costs linked to the study: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Investigator fees: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Leadership role: F. Hoffmann-La Roche Ltd.; Financial Interests, Institutional, Other, Honoraria: F. Hoffmann-La Roche Ltd., Bayer; Financial Interests, Institutional, Research Grant, Institutional research funding: Merck, Bayer; Financial Interests, Personal, Other, Travel/accommodation/expenses: F. Hoffmann-La Roche Ltd., Celgene, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board, Advisory consultant: F. Hoffmann-La Roche Ltd., Daiichi Sankyo, BMS, AbbVie; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.