Baseline tumor size (BTS) is a known predictor of response to anti-PD(L)1 immune checkpoint inhibitors (ICI) in melanoma and NSCLC patients (pts), with lower BTS predicting better treatment outcome. However, no data are currently available on the role of BTS in other solid tumors as well as for next-generation immuno-oncology agents (NGIO).
We reviewed data of pts with any solid tumor consecutively treated at our institution from August 2014 to March 2019, receiving ≥1 dose of ICI and/or NGIO within phase 1 trials. Included drugs, alone or variously combined, were: monoclonal antibodies (mAb) targeting PD(L)1, CTLA4, LAG3, GITR, TIM3, NGK2A, CSF1R, anti-FAPα IL2v, bispecific anti-PD1/TGFß mAb, anti- IDO1 small molecule, intralesional oncolytic peptides or TLR7-agonist. BTS was calculated as ∑iRECIST 1.1 baseline target lesions. Pts were divided into two groups according to BTS (≤median, >median). Differences in terms of overall response rate (ORR), clinical benefit rate at 6 months (CBR6) and progression-free survival (PFS) were compared.
150 pts were included in the analysis with: breast, ovarian, head & neck, colorectal, lung, mesothelioma, melanoma, pancreatic, uterine/cervical, transitional cell and other cancer types. 22 pts were pretreated with ICI. Median BTS was 79 mm (range 10-313); baseline LDH was more frequently elevated in pts with high BTS (68% vs 30%, p<0.001). Pts with low BTS achieved higher ORR (23% vs 4%, p<0.001), higher CBR6 (37% vs 14%, p<0.001) and longer median PFS (3.6 vs 1.9 months; p<0.001) compared with the high BTS group. By restricting the analysis to pts receiving a study regimen including an anti-PD1 agent (n=115), the benefit remained consistent, with higher ORR (31% vs 5%, p=0.002), numerically higher CBR6 (43% vs 17%, p=0.28) and longer median PFS (4.7 vs 2.1 months, p<0.001) in the low BTS group. The benefit was also significant in pts receiving NGIO for more immunogenic tumors (with at least 1 EMA approved ICI before March 2019) (n=55): higher ORR (45% vs 11.5%, p=0.006), numerically higher CBR (52% vs 23%, p=0.29) and longer median PFS (7 vs 2,3 months; p=0.003) in pts with low BTS.
Lower BTS is associated with better treatment outcome in pts with any solid tumor treated with NGIO.
The authors.
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C. Criscitiello: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self): Lilly; Honoraria (self): novartis; Honoraria (self), Advisory/Consultancy: Roche. G. Curigliano: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Ellipses Pharma; Honoraria (self): Foundation Medicine; Honoraria (self): Samsung. All other authors have declared no conflicts of interest.