TABLE A8.
Summary of Resistance Mechanisms in End-of-Treatment ctDNA Samples
| Resistance Mechanism | Lorlatinib (n = 31) | Crizotinib (n = 89) |
|---|---|---|
| Resistance mechanisms, No. (%) | ||
| New single ALK mutation | 0 | 8 (9) |
| ALK compound mutation | 0 | 2 (2) |
| Bypass mechanism, No. (%) | 9 (29) | 10 (11) |
| MAPK pathway aberration | 3 (10) | 1 (1) |
| PI3K/MTOR/PTEN pathway aberration | 2 (6) | 0 |
| RTK pathway aberration | 4 (13) | 5 (6) |
| Cell cycle pathway aberration | 2 (6) | 5 (6) |
| Other gene aberration, No. (%) | 11 (35) | 19 (21) |
| Unknown, No. (%) | 13 (42) | 56 (63) |
NOTE. Resistance mechanisms at EOT were not available for three patients because of results not reported at screening and for one patient because of results not reported at screening and EOT. The following aberrations were identified: MAPK pathway aberration: Lorlatinib: KRAS G12C; BRAF G466E; BRAF amplification; Crizotinib: KRAS K117N. PI3K/MTOR/PTEN pathway aberration: Lorlatinib: PIK3CA amplification; PTEN Q214*. RTK pathway aberration: Lorlatinib: MET amplification (3); EGFR amplification; Crizotinib: NCOA4-RET fusion; EGFR L858R; FGFR1/PDGFRA amplification; EGFR amplification; FGFR3 Y770F. Cell cycle pathway aberration: Lorlatinib: MYC amplification; RB1 K80*; Crizotinib: CDK4 amplification; CDK6 amplification; CDKN2A Y44fs; RB1 M695fs; CCND2 I287T. Other gene aberration: Any alteration in any of the other genes included in the G360 panel (eg, APC, AR, ARID1A, ATM, etc).
Abbreviations: ctDNA, circulating tumor DNA; EOT, end of treatment.