Table 1.
Immune checkpoint inhibitors (ICI) in RET-altered cancersa
| Study | MSKCC retrospective study [63] | MDACC retrospective study [62] | Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic database (CGD) and Guardant Health database (GHD) [64] |
|---|---|---|---|
| Number of patients | 74 | 70 | 29 in CGD, 40 in GHD |
| Tumor types | RET-rearranged lung cancers | RET-altered solid tumors; NSCLC (n = 29), MTC (n = 32), DTC and other cancers (n = 9) | RET fusion-positive NSCLC |
| Smoking history | 31% tobacco exposure | 29% tobacco exposure | 12/29 tobacco exposure |
| RET fusion partner |
KIF5B (58%) CCDC6 (16%) |
Fusion (49%) - KIF5B (41%) Mutation (51%) - M918T (67%) |
KIF5B (74%) CCDC6 (14%) |
| Immune phenotype findings in available population | PD-L1 expression: zero (58%), 1–49% (23%) Tumor mutational burden (TMB) - RET-rearranged (1.75 Mut/Mb) versus RET wild-type (5.27 Mut/Mb) (P < 0.0001) |
PD-L1 expression: weak (<1%) (56%), 1–49% (22%) Tumor mutational burden (TMB) - All 15 patients have TMB low (≤5 Mut/Mb) |
PD-L1 expression: <1% (7/13), ≥1% (6/13), others missing Tumor mutational burden (TMB) - <6 Mut/Mb (11/14) - ≥6 Mut/Mb (3/14) - Others missing |
| Response in evaluable patients | Response was not observed (n = 13) - SD 3/13 (23%), PD 8/13 (62%), mPFS 3.4 months |
Time to treatment discontinuation (TTD) - Non-ICI group (18 months) versus ICI group (5.2 months) (P = 0.00045) |
Median real-world PFS of 4.2 months and OS of 19.1 months (CGD) |
a
Abbreviations: DTC, differentiated thyroid cancer; MDACC, MD Anderson Cancer Center; mPFS, median progression-free survival; MSKCC, Memorial Sloan-Kettering Cancer Center; MTC, medullary thyroid cancer; Mut/Mb, mutations per mega base; NA, not available; NSCLC, non-small cell lung cancer; PD, progressive disease; PD-L1, programmed death-ligand 1; SD, stable disease.