124MO - A single centre experience of patients with rare cancers referred for early phase clinical trials

Background

Cancers affecting <6/100,000/year are classified as rare, but they account for almost 25% of all cancers. They have worse 5-year survival than more common cancers and limited treatment options. Early-phase clinical trials (EPCT) have evolved with novel designs and the increasing use of precision medicine and molecular profiling. Therefore, EPCTs may represent a potential treatment option for patients with rare cancers.

Methods

We conducted a retrospective study of patients with a rare cancer referred to a large EPCT team at a UK specialist centre over a 5-year period (2016-2020). Data collection included patient demographics, medical and oncological history, genomic variants, EPCT participation and associated response and survival outcomes.

Results

We included 240 patients with a rare cancer. The mean age at diagnosis was 51.7 years (range 16-84), 54.2% of the patients were female. The most frequent rare cancer originated from the digestive system (27.1%), female genital tract (20%) and head and neck (H+N) (18.3%). At the time of referral, 86.2% of the patients had at least one site of distant metastasis while 190 patients (79.2%) had received at least one line of systemic anticancer treatment. Molecular profiling was offered to 45.5% of the population, median number of gene alterations was 3 per patient (range 1-20) and genes most commonly mutated were TP53 (43.4%), PIK3CA (24.1%), and KRAS (15.7%). 51 patients participated in EPCTs, with 39.2% achieving SD and 11.8% PR. Median OS in the trial patients was 44 months (95% CI 30.1 – 57.90) and 32 months (95% CI 27.63 – 36.37) for patients whom did not participate in an EPCT (p = 0.009, HR 0.62). Patients with sarcomas had the longest median OS (46 months), followed by patients with H+N cancers (39 months) and NETs (35 months). Good Royal Marsden Hospital (RMH) prognostic score (0-1) was correlated with favourable survival when controlling for age and gender (HR 0.67, 95% CI 0.46 – 0.96, p = 0.03).

Conclusions

Participation of rare cancer patients in EPCTs may be associated with a survival benefit and potentially lead to the development of new treatments for these patients. Moreover, expanded use of precision medicine is paramount as it can offer crucial information for treatment selection in this heterogenous group.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N. Cook: Financial Interests, Institutional, Invited Speaker: Roche, Taiho, AstraZeneca, RedX, Orion, Avacta, Bayer, Eisai, UCB, Starpharma, Boehringer Ingelheim, Stemline, Ergomed; Non-Financial Interests, Personal, Advisory Role: Roche. D.M. Graham: Financial Interests, Personal, Advisory Board, Consulting role on advisory board: Clinigen; Financial Interests, Personal, Invited Speaker: Cancer Drug Development Fund; Financial Interests, Personal, Advisory Board: McCann Health; Financial Interests, Institutional, Invited Speaker, Institutional funding from study: MSD, Codiak Biosciences, Starpharma, Faron Pharmaceuticals, Synthon, Janssen; Financial Interests, Institutional, Other, Sub-I: Institutional funding from study: AstraZeneca, Roche, BerGenBio, GlaxoSmithKline, Bayer, Bicycle Pharmaceuticals, Carrick, Taiho Pharmaceuticals, CytomX Therapeutics, RedX Pharma PLC, Eisai Inc., Octimet, Orion Pharma, Kinex Pharmaceuticals, Boehringer Ingelheim, BMS, Turning Point Therapeutics, Immutep, Agalimmune, Kymab, Blueprint, Astellas, Cellcentric, UCB Biopharma USL, Eli Lilly, Seagen, Repare Therapeutics, Timepoint Therapeutics, Astex, Stemline, Crescendo Biologics Ltd., ADC Therapeutics, Genentech, Avacta Life Sciences Ltd., Nurix Therapeutics Inc.; Financial Interests, Institutional, Other, Sub-I: Institutional finding from study: Chugai Pharmaceuticals; Financial Interests, Institutional, Invited Speaker: Incyte. M.G. Krebs: Financial Interests, Personal, Advisory Board: Bayer, Roche, Janssen, Guardant Health; Financial Interests, Personal, Invited Speaker: Roche, Janssen; Financial Interests, Institutional, Expert Testimony: AstraZeneca; Financial Interests, Institutional, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Blueprint, Astex, Bayer, BerGenBio, Carrick, Immutep, Janssen, Novartis, Nurix, Nuvalent, Pyramid Biosciences, Roche, Seattle Genetics, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Novartis; Other, Personal, Other, Travel expenses for congress: Immutep, Janssen. F. Thistlethwaite: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, Adboard/consultancy: T-Knife Therapeutics; Financial Interests, Personal, Advisory Board: Adicet, Janssen, EnaraBio, Immatics, Ixaka, Scenic Biotech, F-Star, Leucid; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Kite Gilead; Financial Interests, Personal, Other, Occasional individual consulting: Guidepoint; Financial Interests, Institutional, Other, iMATCH is a 12 partner consortium funded by not for profit Innovate UK (UK government body) partners include commercial, clinical and academic institutes. I am director and my salary (0.1WTE) is supported through this work as a grant to my institution (The Christie NHS foundation trust - not for profit NHS hospital) from IUK: iMATCH director; Financial Interests, Institutional, Officer, Clinical lead for this 10 partner consortium of clinical academic and commercial partners. My salary is partly supported (approx. 0.05WTE) through this by a grant paid by Innovate UK (a NFP government body) to my institution (The Christie NHS foundation trust a NFP UK hospital): SAMPLE; Financial Interests, Institutional, Invited Speaker, NCT02890069: Novartis; Financial Interests, Institutional, Research Grant, Sarcoma pathways project: GSK; Financial Interests, Institutional, Invited Speaker, NCT02493751: Pfizer; Financial Interests, Institutional, Invited Speaker, NCT03245736, NCT02988817, NCT02552121, NCT02001623: GenMab; Financial Interests, Institutional, Invited Speaker, NCT02277717: Synthon; Financial Interests, Institutional, Invited Speaker, NCT03013491: CytomX; Financial Interests, Institutional, Invited Speaker, NCT03314935: Incyte; Financial Interests, Institutional, Invited Speaker, NCT02908906: Janssen; Financial Interests, Institutional, Invited Speaker, NCT03132792, NCT04044768: Adaptimmune; Financial Interests, Institutional, Invited Speaker, NCT03400332: BMS; Financial Interests, Institutional, Invited Speaker, NCT04262466, NCT03973333, NCT03515551: Immunocore; Financial Interests, Institutional, Invited Speaker, EudraCT Number: 2018-001005-85, 2018-003446-16: Achilles Ltd.; Financial Interests, Institutional, Invited Speaker: Agalimmune Ltd.; Financial Interests, Institutional, Invited Speaker, NCT02834247: Millenium Pharmaceuticals/Takeda; Financial Interests, Institutional, Invited Speaker, NCT02690350: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, NCT04839991: Crescendo; Financial Interests, Institutional, Invited Speaker, NCT05104515: Oxford Vacmedix Ltd.; Financial Interests, Institutional, Invited Speaker, NCT05278975: RS Oncology LLC; Financial Interests, Institutional, Invited Speaker, NCT03697824, NCT03391778: GSK; Financial Interests, Institutional, Invited Speaker, NCT04140500, NCT04857138, NCT04826003: Roche; Financial Interests, Institutional, Invited Speaker, NCT04272203: AbbVie; Financial Interests, Personal, Invited Speaker, NCT05008913, NCT04949425, NCT0331509, NCT03313557: AstraZeneca; Financial Interests, Institutional, Invited Speaker, NCT03829501: Kymab Ltd./Sanofi; Financial Interests, Institutional, Invited Speaker, EudraCT ID No: 2019-003329-11: Chugai; Financial Interests, Institutional, Invited Speaker, NCT05430555: T-Knife Therapeutics; Financial Interests, Institutional, Invited Speaker, NCT03621982: ADCT Therapeutics; Financial Interests, Institutional, Research Grant, IRAS Project ID: 227414: Novartis; Non-Financial Interests, Personal, Other, Panel member for a funding committee (MRC is a UK government NFP organisation): MRC DPFS panel member; Non-Financial Interests, Personal, Advisory Role, Sarcoma UK is a not-for-profit charity. I act as an advisor on their Research Strategy Committee. This role is not compensated: Sarcoma UK; Non-Financial Interests, Personal, Leadership Role, Funding is from not-for-profit government bodies. Role is not compensated: Chair of the Independent Steering Committee for NIHR Blood & Transplant Research Unit, Oxford; Non-Financial Interests, Personal, Advisory Role, Funding panel member for CRUK (not-for profit charity). Role is not compensated: CRUK New Agents Committee Member; Non-Financial Interests, Personal, Leadership Role, Chair of Cell therapy subgroup. MRC is a not-for-profit organisation. Role is not compensated: MRC Advanced Therapies Task Group. L. Carter: Financial Interests, Personal, Other, Consultancy: Bicycle Therapeutics, Boehringer Ingelheim, Athenex; Financial Interests, Personal, Full or part-time Employment, Medical Advisor: Cancer research UK Centre for Drug Development; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, Bicycle Therapeutics, Cellcentric, Eli Lilly, Athenex, Lupin Limited, Repare Therapeutics, Cytomx therapeutics, EMD Serono/Merck KGaA, Sierra Oncology. All other authors have declared no conflicts of interest.