200P - Outcomes of patients (pts) with unfavourable, non-squamous cancer of unknown primary (CUP) progressing after induction chemotherapy (CTX) in the global, open-label, phase II CUPISCO study

Background

CUPISCO (NCT03498521) assesses comprehensive genomic profiling (CGP)-based molecularly guided therapy (MGT) in pts with newly diagnosed, unfavourable, non-squamous CUP. CGP-based MGT significantly improved progression-free survival (PFS) over continued CTX in pts with disease control after 3 cycles of standard first-line platinum-based induction CTX (category 1). Pts with progressive disease (PD) post-induction CTX (category 2) received MGT. We report outcomes of category 2 pts.

Methods

MGT was investigator-chosen from 12 regimens after discussion of CGP at a molecular tumour board. Pts with actionable targets post-CGP received targeted therapy or atezolizumab (atezo) monotherapy. If no targeted option was available, pts continued CTX with addition of atezo. Primary endpoint: PFS; secondary endpoints included overall survival (OS). Results are descriptive.

Results

Data cut-off was 14/02/23. 135/573 pts reaching the end of induction (24%) had PD and were thus assigned to category 2. 92 (68%) of these pts received ≥1 dose of study drugs post-PD. One pt received CTX only and 91 received MGT. 23/91 pts (25%) had an actionable target, of whom 12/23 (52%) received atezo monotherapy. 68/91 pts (75%) received atezo + CTX. Overall, median PFS and OS were 2.1 (95% confidence interval 2.0–2.7) and 6.0 (4.6–8.7) months, respectively. Median PFS was 2.1 (2.0–7.7) vs 2.1 (2.0–2.8) months and median OS was 14.0 (5.3–24.3) vs 5.2 (4.2–8.4) months, for pts with or without actionable targets, respectively.

Conclusions

Overall, prognosis of pts with unfavourable CUP and PD after induction CTX is dismal, with most experiencing further PD by time of first restaging after 3 months. PFS effects observed for MGT in CUPISCO category 1 pts with an actionable target could not be achieved in category 2 pts with an actionable target. These findings argue for early use of MGT in CUP. However, a trend towards improved OS in pts with an actionable target suggests that a subgroup benefits from MGT despite post-PD post-induction CTX. More research is needed to confirm these results due to limited numbers of pts.

Clinical trial identification

NCT03498521/13 April 2018.

Editorial acknowledgement

Research support for third-party editing assistance for this abstract, furnished by Daniel Clyde, PhD, of Nucleus Global, an Inizio Company, 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

T. Bochtler: Financial Interests, Institutional, Research Grant, Institutional research funding: 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, Institutional, Other, Works as study oncologist for the CUPISCO trial, and has received coverage for study-related travels and remuneration for study-related work in the Molecular Tumour Board for the benefit of his employer: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. 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. C. Pauli: Financial Interests, Personal, Other, Travel/accommodation/expenses: 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; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. 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, Institutional, Invited Speaker: Bayer, Amgen, Teva, Lilly, Johnson & Johnson; Financial Interests, Institutional, Advisory Board, Personal, Honororia: Novartis; Financial Interests, Institutional, Advisory Board: Merck, AstraZeneca, Janssen (Johnson & Johnson), Teva; Financial Interests, Institutional, Advisory Board, Honororia: Astellas, Pfizer; Financial Interests, Personal, Advisory Board, Honororia: Bristol Myers Squibb, Amgen, MSD; Financial Interests, Institutional, Invited Speaker, Honororia: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Honororia: Astellas, AstraZeneca; Financial Interests, Personal, Other, Travel support: Amgen; Financial Interests, Institutional, Local PI: Novartis, BMS, Merck, AstraZeneca, Nektar, Janssen (Johnson & Johnson), Amgen, Bayer, Incyte, MSD; Financial Interests, Institutional, Local PI, Personal: Lilly; Financial Interests, Personal and Institutional, Local PI: Roche, Sanofi, Yuhan, Henlius, Pfizer; Non-Financial Interests, Principal Investigator: Roche. F. Bigot: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Sanofi, MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD; Other, Travel/accommodation/congress: 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, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Local PI: Taiho, Roche, AstraZeneca, Avacta, Bayer, Eisai, UCB, Boeringher, Stemline; Financial Interests, Institutional, Coordinating PI: RedX, Orion, Starpharma, Loxo-Oncology; Non-Financial Interests, Advisory Role: Roche; Non-Financial Interests, Other, Committee chair: Cancer Research UK. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: 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; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, AstraZeneca; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. N. Ma: Financial Interests, Personal, Full or part-time Employment, Employee: Genentech, Inc; 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. M. Ozguroglu: Financial Interests, Personal, Advisory Board: Janssen, Sanofi, Astellas, Regeneron, MSD; 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, Regeneron, MSD; Financial Interests, Personal, Other, Travel support: BMS, Janssen, AstraZeneca, Regeneron; Financial Interests, Personal, Other, Speaker support: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Regeneron; Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. R.A. Pazo Cid: Non-Financial Interests, Personal, Advisory Board, Advisory Role: Servier, Bristol Myers, 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; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. 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 using Foundation Medicine 1: Roche; Financial Interests, Personal, Advisory Board, Advisory Board on Lonsurf for chemorefractory mCRC in readiness for NICE application: Servier; Financial Interests, Personal, Advisory Board, For advising on latest trial data on dostarlimab for future trial designs and combinations: GSK; Financial Interests, Personal, Advisory Board, Advising on company IMP for trial expansion/new trial designs, as well as market access in UK.: Seagen; Financial Interests, Institutional, Local PI, For MATTERHORN Trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, 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, Local PI, UCLH PI for LEAP 15 and MK4280A-007 trials: MSD; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator for NOUS209-001 trial: Nouscom; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator for CUPSICO trial: Roche; Financial Interests, Personal, Steering Committee Member, Steering Committee Member of CUPISCO trial: Roche; Financial Interests, Institutional, Local PI, PI to run BNT 122 trial-01: BioNTech; Non-Financial Interests, Member: ASCO, Association of Cancer Physicians UK. P. Arni: 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 writing assistance: F. Hoffmann-La Roche Ltd. H. Moch: 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, Advisory Board, Advisory Consultant: F. Hoffmann-La Roche Ltd, Definiens, Bayer, Ipsen, Amgen; Financial Interests, Personal, Other, Travel/accommodation/expenses: F. Hoffmann-La Roche Ltd, Definiens; Financial Interests, Institutional, Research Grant, Institutional research funding: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. L. Mileshkin: Financial Interests, Personal, Advisory Board, Participation in Dostarlimab advisory board: GSK; Financial Interests, Institutional, Coordinating PI, Institutional funding from BeiGene for an investigator-initiated trial: BeiGene; Financial Interests, Personal, Coordinating PI, Support for flights to attend ESMO meetings in Madrid and Singapore to present results of the CUPISCO trial: Roche; Financial Interests, Personal, Other, Medical writing support for publications related to the CUPISCO trial: Roche; 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.