Table 1.

Characteristics of the osimertinib-resistant cohort and the patients with fusion-positive EGFR-mutant NSCLCs

Characteristics of the osimertinib-resistant cohort (patients 1–41)
Factorn (%) unless otherwise noted
Gender
 Male15 (37)
 Female26 (63)
Age (years), median (range)64 (40–87)
Founder EGFR mutation
 Exon 19 deletion23 (56)
 L858R18 (44)
Duration of osimertinib treatment (months), median (range)11.6 (1–32.7)
Prior lines of therapy
 01 (2)
 116 (39)
 2 or more24 (59)
Treated with another third-generation EGFR TKI pre-osimertinib
 Rociletinib12 (29)
 Nazartinib2 (5)
 ASP82731 (2)
 None26 (63)
Type of post-osimertinib biopsy
 Tissue only15 (37)
 Plasma only9 (22)
 Both tissue and plasma17 (41)
Number of post-osimertinib tissue biopsies
 One29 (91)
 Two3 (9)
Characteristics of the patients with fusion-positive EGFR-mutant NSCLC
Patient IDaInstitutionT/PbTestingcAcquired fusionFounder EGFR mutationTreatment history prior to detection of fusionT790M statusdOther molecular findingsdTreatment after fusion detectionResponse (RECIST 1.1)
1MGHTSFACCDC6–RETDel191. AfatinibOsimertinib + BLU-667PR (−78%)
2. Osimertinib
2MGHTSFAPCBP2–BRAFDel191. ErlotinibTP53
2. Carbo/pem
3. Osimertinib
3MGHTFOAGK–BRAFDel191. ErlotinibCTNNB1, APC, CDKN2A/B
2. Osimertinib
33MGHPG360CCDC6–RET + TPM3–NTRK1Del191. ErlotinibEGFRAmp, BRAFAmp, METAmp, CKD6Amp, CCNE1Amp, TP53, TERT
2. Osimertinib
42MGHTSFACCDC6–RETDel191. Cisplatin/pemetrexedTP53Afatinib + cabozantinibSD (−6%)
2. Afatinib
43MGHTSFABAIAP2L1–BRAFDel191. Erlotinib+SMAD4, PTCH1, TP53
2. Osimertinib
3. Carbo/pem
4. Osimertinib/gemcitabine
44UC-IrvineTSFANCOA4–RETDel191. Cisplatin/pemetrexed (adjuvant)RNF43, CDKN2AOsimertinib + BLU-667PR (−78%)
2. Afatinib/cetuximab
  • Abbreviations: PR, partial response; SD, stable disease.

  • aPatients 1–41 correspond to patients in the osimertinib-resistant cohort, with molecular findings shown in Fig. 1. Patients 42, 43, and 44 are not included in Fig. 1 because their biopsies were obtained at progression on therapies other than single-agent osimertinib.

  • bT, tissue testing (from biopsies of progressing lesions); P, plasma ctDNA testing (as indicated in next column).

  • cTesting: SFA, MGH Solid Fusion Assay; FO, FoundationOne NGS Panel; G360, Guardant 360 ctDNA NGS Panel.

  • dT790M and other molecular findings refer to the time of fusion detection.