29O - Clinical characterization of long-term survivors in phase I clinical trials

Background

Retrospective comparations between cohorts of patients (pts) included in early clinical trials show an increase in response rates from 5% to 19% in some series. Nevertheless, pts achieving long-term survival has been poorly understood and characterized. Some prognostic scores have been proposed to exclude patients with low probability to achieve overall survival (OS) at 90 days, but the role of prognostic scores to predict long-term survivors (LTS) is poorly understood.

Methods

A retrospective observational case-control study of pts treated with immunotherapy or targeted therapy at VHIO’s phase I unit between 2013 and 2023 was conducted. Pts with a OS >3 years (y) after C1D1 were categorized as LTS and compared to short-term survivors (STS) with OS <3y as consecutive controls. Clinical, histopathologic, PIPO score, and treatment were collected. Comparisons between LTS and STS were made with Pearson’s Chi-Squared test or Fisher’s exact test for categorical variables and Wilcoxon rank sum test for continuous variables.

Results

Of 799 pts, a total of 89 pts (11%) were classified as LTS. Median OS was 5.1y (IQR 3.6-6.3) for LTS and 0.7 yrs (IQR 0.4-0.8) for STS. LTS were like STS in age (61 yrs vs 63 yrs) ECOG (40% vs 48% had ECOG ≥1), and sex (55% vs 56%) [p>0.05]. Most common tumor types among LTS were HNSCC (18%), melanoma (10%), and breast (10%) and for STS were CRC (28%), breast (13%), and melanoma (11%). Number of previous lines (≥3) in 21 pts (24%) for LTCS and 43 pts (44%) for STS (p=0.03). Visceral mets were present in 58% of LTS and 75% of STS (p=0.015) whereas no differences in ganglionar or bone mets were present (p>0.05). LTS received higher proportion of molecular-matched treatment (14 vs 0%) and checkpoint inhibitors (37 vs 5%) [p<0.001]. Higher level of leukocytes, neutrophil count, and dNLR was related to STS whereas higher albumin levels to LTS (all p<0.05). ORR (CR+PR) was 56% in LTS and only 12% for STS (p<0.001). A poor prognosis PIPO score (5-6 points) was present in 38% of STS vs 11% of LTS (p<0.001) while 60% of LTS had PIPO score of 1-2 vs 32% of STS pts.

Conclusions

Long-term survival is an achievable goal for a significant number of patients included in early phase clinical trials. A deeper understanding of clinical and molecular variables may improve patient selection strategies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

VHIO.

Funding

La Caixa.

Disclosure

O. Mirallas: Financial Interests, Personal, Invited Speaker: ROVI; Financial Interests, Institutional, Invited Speaker: Roche, Merck; Other, Personal, Other, Travel Expenses: Kyowa Kirin, Almirall; Other, Personal, Other, Travel Expenses and Conference Fee: Sanofi. A. Hernando Calvo: Other, Personal, Other, Travel support: Merck Serono, Kyowa Kirin. I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, eTheRNA Immunotherapies, Merck Sharp & Dohme (MSD), Rakuten Pharma, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Personal, Expert Testimony: Cancer Expert Now, Merck Serono, Boehringer Ingellheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GSK, Gliknik, Incyte, ISA pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics, Gilead; Non-Financial Interests, Personal, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Personal, Member, Head and Neck Group: EORTC; Non-Financial Interests, Personal, Member: SEOM, ASCO. R. Dienstmann: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, Ipsen, Libbs, Lilly, Merck Sharp & Dohme, Roche, Sanofi, Servier, GSK, Takeda, Janssen, Foundation Medicine; Financial Interests, Personal, Advisory Board: Bayer, Roche; Financial Interests, Personal, Full or part-time Employment, Oncoclínicas is a private healthcare provider in Brazil. I work part time as Medical Director of the Precision Medicine and Big Data Initiative. We develop molecular tests (pathology and genomics) that are offered to patients treated in the organisation as part of support programs sponsored by pharmaceutical companies and I coordinate research activities with real-world clinico-genomics cohorts: Oncoclínicas; Financial Interests, Personal, Stocks/Shares: Trialing; Financial Interests, Personal, Research Grant: Merck. M. Vieito Villar: Non-Financial Interests, Personal, Principal Investigator: Roche, BMS, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. E. Garralda: Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte; Financial Interests, Personal, Invited Speaker: MSD, Lilly, Roche, Thermo Fisher, Novartis, Seagen; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Institutional Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. All other authors have declared no conflicts of interest.