Abstract 1046P
Background
IO-based therapies have been approved based on clinical trials that have strict eligibility criteria. Although these data are extrapolated to the general population, the outcomes of trial ineligible patients are poorly characterized.
Methods
Using the International mRCC Database Consortium and Alberta Immunotherapy Database, patients with advanced renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) or melanoma treated with 1L PD-(L)1 inhibition +/- tyrosine kinase inhibitor (RCC), chemotherapy (NSCLC) or CTLA-4 inhibitor (RCC/Melanoma) were included. Trial eligibility was retrospectively determined according to commonly used exclusion criteria. Outcomes were response rate, time to treatment failure (TTF) and overall survival (OS).
Results
31% (373/1200) of patients were deemed trial ineligible (38%, 37%, and 25% were RCC, NSCLC and melanoma, respectively). The reasons for ineligibility were: KPS < 70%/ECOG > 1 (40%, 149/373), brain metastases (32%, 119/373), Hb < 9 g/dL (16%, 60/373), eGFR < 40 mL/min (16%, 58/373), platelet < 100,000/mm3 (1%, 5/373), neutrophil < 1500/mm3 (1%, 5/373) and no clear-cell component (RCC only; 13%, 48/373). Outcomes are listed in the table. Between ineligible vs. eligible patients, the adjusted HR for death in RCC (by hypercalcemia, diagnosis to therapy < 1 yr, neutrophilia, thrombocytosis), NSCLC (by LDH, neutrophil to lymphocyte ratio), and melanoma (by LDH, M1c/M1d status) was 1.66 (95% CI 1.11-2.49), 2.63 (95% CI 1.80-3.85) and 1.55 (95% CI 1.03-2.32), respectively.
Conclusions
31% of real-world patients treated with contemporary 1L IO-based therapies were ineligible for clinical trials. These patients were older and had inferior TTF and OS compared to trial eligible patients. These data may guide patient counseling and temper expectations of benefit. Greater effort is required to understand the gap between trial efficacy and real-world effectiveness (Table). Table: 1046P
| Age, sex and clinical outcome | Trial ineligible (n=373) | Trial eligible (n=827) | P-value |
| Median age | 67 | 65 | 0.02 |
| Male | 57% (213/373) | 66% (544/827) | < 0.01 |
| ORR %, (n/n) | 36% (96/266) | 46% (317/690) | < 0.01 |
| RCC | 32% (36/113) | 44% (138/315) | 0.03 |
| NSCLC | 29% (25/87) | 37% (68/184) | 0.18 |
| Melanoma | 53% (35/66) | 58% (111/191) | 0.47 |
| Median TTF (mon) (95% CI) | 2.6 (2.1-3.4) | 6.4 (5.5-7.6) | < 0.01 |
| RCC | 3.7 (2.5-5.5) | 7.8 (6.2-9.7) | < 0.01 |
| NSCLC | 2.1 (1.4-3.0) | 6.4 (5.1-9.7) | < 0.01 |
| Melanoma | 2.5 (1.4-3.9) | 4.9 (4.1-6.1) | < 0.01 |
| Median OS (mon) (95% CI) | 11.8 (8.8-15.3) | 35.1 (30.5-42.5) | < 0.01 |
| RCC | 25.1 (15.1-40.2) | 42.5 (32.5-54.8) | < 0.01 |
| NSCLC | 5.5 (4.1-7.7) | 21.9 (16.2-NR) | < 0.01 |
| Melanoma | 10.1 (5.6-17.7) | 38.2 (23.2-NR) | < 0.01 |
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Daniel Y.C. Heng.
Funding
Has not received any funding.
Disclosure
J.C. Wells: Travel/Accommodation/Expenses: Pfizer. J. Monzon: Advisory/Consultancy: Amgen BMS Merck Novartis Sanofi; Research grant/Funding (self), Research grant/Funding (institution): Merck. N.S. Basappa: Honoraria (self), Honoraria (institution), Advisory/Consultancy: BMS, Merck, Pfizer, EMD Serono, Roche, Eisai, Ipsen, AstraZeneca. S.K. Pal: Advisory/Consultancy: Pfizer, Novartis, Aveo, Myriad Pharmaceuticals, Genentech, Exelixis, Bristol-Myers Squibb, Astellas Pharma, Ipsen, Eisai; Honoraria (self), Honoraria (institution): Novartis, Medivation, Astellas Pharma; Research grant/Funding (self), Research grant/Funding (institution): Medivation. F. Donskov: Research grant/Funding (institution): Pfizer, Ipsen. T.K. Choueiri: Advisory/Consultancy: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Prometheus Laboratories, Alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aven; Leadership role: Dana Farber Cancer hospital, NCCN, Kidney cancer Association, KidneyCan, ASCO; Non-remunerated activity/ies, Medical writing and editorial assistance support may have been funded by Communications companies funded by pharmaceutical companies such as: ClinicalThinking, Health Interactions, Envision Pharma Group, Fishawack Group of Companies, Parexel; Shareholder/Stockholder/Stock options: Pionyr, Tempest Therapeutics; Honoraria (self), Honoraria (institution): NCCN, UpToDate, Michael J. Hennessy Associates, ASCO, Harborside Press, Analysis Group, AstraZeneca, Alexion Pharmaceuticals, Sanofi/Aventis, Bayer, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Peloton Therapeutics, Pfizer, Cor; Research grant/Funding (self), Research grant/Funding (institution): Pfizer, Novartis, Merck, Exelixis, Tracon Pharma, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Peleton Therapeutics, Roche/Genentech, Celldex, Agensys, Eisai, Takeda, Prometheus, Ipsen, Corvus Pharmaceuticals, Cerulean Pharma, Seattle Genetics/Ast. D.Y.C. Heng: Advisory/Consultancy: Pfizer, Novartis, Bristol-Myers Squibb, Janssen, Astellas Pharma, Ipsen, Eisai, Merck; Research grant/Funding (institution): Pfizer, Novartis, Exelixis, Bristol-Myers Squibb, Ipsen. All other authors have declared no conflicts of interest.