96P - The Hammersmith score optimises patient selection and predicts for overall survival in early-phase cancer trial participants independent of tumour burden

Background

Significant anti-tumour response is increasingly seen in early-phase cancer trials (EPCT), requiring optimal patient selection and accurate prognostication. Hammersmith Score (HS), a simple prognostic index derived on routine biochemical measures (Albumin <35g/L, Lactate Dehydrogenase (LDH) >450 U/L, Sodium <135mmol/L) predicts response and survival in EPCT participants. HS has not been validated in the cancer immunotherapy era.

Methods

We retrospectively analyzed characteristics and outcomes of 212 referrals to our early-phase unit (12/2019-12/2022). Independent predictors for overall survival (OS) were identified from univariable (Kaplan Meier) and multivariable (Cox regression). HS was calculated for 66 patients and compared with the Royal Marsden Score (RMS) to predict OS and 90-day mortality (90DM). Multivariable logistic regression and ROC curves were used to estimate 90DM and c-index was used to compare prognostic models.

Results

Of 212 referrals, 147 patients were screened and 82 patients treated. Median age 62.1 years (52.2-71.9); median OS 7.3 months (95% CI: 6.2-8.4); 45.1% male; 63.4% performance status ≥1, median number of metastatic sites was 2. Experimental therapies included immunotherapy (n=53), targeted therapy (n=6) and chemotherapy (n=23). Prognostic stratification by HS identifies significant difference in median OS: 11.28 months for HS0 (95%CI: 8.7-13.8), 5.29 months for HS1 (95%CI: 2.0-8.6) and 1.2 months for HS2-3 (95% CI: 1.0-1.3, p<0.001). ROC analysis showed HS and RMS perform similarly in predicting 90DM (AUROC 0.59 and 0.56 respectively). HS was confirmed as a multivariable predictor for OS (HR: HS1 vs. 0 2.6 (95%CI: 1.1-6.3), p=0.030; HS 2/3 vs. 0: 8.5 (95%CI: 1.9-37.4), p=0.005, C-index 0.775) with similar multivariable predictive ability as RMS (HR: RMS 2 vs. 0/1 7.8 (95%CI: 2.1-28.6), p=0.002; HS3 vs. 0/1 11.1 (95%CI: 2.9-42.5), p<0.001, C-index 0.741).

Conclusions

HS is a validated prognostic index for patients with advanced cancer treated in the context of modern EPCTs, independent of tumour burden, removing the need for quantification during patient selection. HS is a simple, inexpensive selection tool to optimise referral for EPCT.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

D.J. Pinato.

Funding

Has not received any funding.

Disclosure

B. Scheiner: Financial Interests, Personal, Other, Travel support: AbbVie, Ipsen, Gilead. A. D'Alessio: Financial Interests, Personal, Other, Travel support and consultancy fees: Roche. A. Cortellini: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, OncoC4; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Eisai, BMS. D.J. Pinato: Financial Interests, Personal, Advisory Board: Mina Therapeutics, Eisai, Exact Sciences, MURSLA, H3B, DaVolterra, AstraZeneca, Bayer Healthcare; Financial Interests, Personal, Invited Speaker: BMS, Ipsen, Roche; Financial Interests, Personal, Other, Editor in Chief role: Wiley; Financial Interests, Institutional, Research Grant: BMS, MSD; Non-Financial Interests, Personal, Principal Investigator: Incyte, H3B, Starpharma, Roche, Ribon Therapeutics, Turning Point Therapeutics, Apollomics; Non-Financial Interests, Personal, Other, Charity Trustee: Cancer Treatment and Research Trust. All other authors have declared no conflicts of interest.