Table 2.
Allele-Specific SARMS Analysis of EGFR Mutations in Tumor Samples and Best Clinical Response.*
| Patient No. and EGFR Mutation Status | EGFR Mutation by Sequencing | EGFR Mutation by SARMS Assay† | Duration of Therapy with Tyrosine Kinase Inhibitor‡ | Best Clinical Response | ||
|---|---|---|---|---|---|---|
| Primary Mutation | T790M | Other | mo | |||
| EGFR mutation present | ||||||
|
| ||||||
| 2 | Del T751_I759 insS | None detected§ | No | 18.2¶ | SD | |
|
| ||||||
| 3 | G719S | G719X | Yes | 3.9 | PR | |
|
| ||||||
| 4 | L858R | L858R | No | >36.9 | PR | |
|
| ||||||
| 5 | Del E746_A750 | Del | Yes | 8.6¶ | PR | |
|
| ||||||
| 8 | L861Q | L861Q | Yes | 4.0 | SD | |
|
| ||||||
| 9 | Del E746_A750 | Del | Yes | 6.2 | PR | |
|
| ||||||
| 10 | L858R | L858R | Yes | 8.3 | PR | |
|
| ||||||
| 11 | Del E746_A750 | Del | No | >14.0 | PR | |
|
| ||||||
| 13 | Del E746_A750 | Del | Yes | 8.3 | PR | |
|
| ||||||
| 14 | Del L747_P753 insS | Del | No | 13.5 | PR | |
|
| ||||||
| 15 | Del E746_S752 insV | Del | No | 30.8 | CR | |
|
| ||||||
| 22 | Del E746_A750 | Del | No | >9.2 | PR | |
|
| ||||||
| 23 | L858R | L858R | No | >7.7 | SD | |
|
| ||||||
| 28 | Del E746_A750 | Del | No | 14.9 | PR | |
|
| ||||||
| 29 | L858R | L858R | No | 11.8 | PR | |
|
| ||||||
| 30 | L858R | L858R | No | Del§ | 3.6 | PR |
|
| ||||||
| 31 | G719A | G719X | Yes | Del§ | 3.9 | SD |
|
| ||||||
| 32 | Del E746_A750 | Del | No | >16.7 | SD | |
|
| ||||||
| 33 | Del E746_A750 | Del | No | 11.4 | PR | |
|
| ||||||
| 34 | Del E746_A750 | Del | No | 17.5 | CR | |
|
| ||||||
| 35 | Del E746_A750 | Del | No | 7.6 | SD | |
|
| ||||||
| 36 | L858R | L858R | No | 9.5 | PR | |
|
| ||||||
| 37 | Del L747_T751 | Del | Yes | 9.2 | PR | |
|
| ||||||
| 38 | L858R | L858R | Yes | 6.9 | PR | |
|
| ||||||
| 39 | Del E746_A750 | Del | No | 14.3 | PR | |
|
| ||||||
| 40 | Del E746_A750 insIP | Del | Yes | 11.3 | SD | |
|
| ||||||
| EGFR mutation absent | ||||||
|
| ||||||
| 24 | None (wild type) | None detected | No | 0.7¶ | PD | |
|
| ||||||
| 25 | None (wild type) | None detected | No | None | NA | |
|
| ||||||
| 26 | None (wild type) | None detected | No | 1.2¶ | PD | |
|
| ||||||
| 27 | None (wild type) | None detected | No | 7.5¶ | SD | |
|
| ||||||
| 41 | None (wild type) | None detected | No | >4.4¶ | SD | |
|
| ||||||
| 42 | None (wild type) | None detected | No | None | NA | |
|
| ||||||
| 43 | None (wild type) | None detected | No | 0.7 | PD | |
|
| ||||||
| 44 | None (wild type) | None detected | No | 2.6 | SD | |
The best clinical response was defined according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR denotes complete response, Del deletions in exon 19, NA not applicable, PD progressive disease, PR partial response, SARMS Scorpion Amplification Refractory Mutation System, and SD stable disease.
The SARMS assay groups all variant breakpoints of the in-frame (exon 19) EGFR deletion mutations as a single Del mutation and all mutations at codon 719 as G719X. The presence or absence of T790M is indicated. Other mutations that were identified with the use of the SARMS assay are listed only when they were present.
When the number of months is preceded by “>,” therapy was ongoing.
The mutation identified by sequencing in Patient 2 was not within the detection capacity of the SARMS assay. In Patients 30 and 31, a second activating EGFR allele was detected at low frequency (other), in addition to the prevalent activating mutation (primary mutation).
In these patients, either gefitinib or erlotinib was administered as second-line or third-line therapy. In all other patients, the drugs were administered as first-line therapy for advanced cancers.