Supplementary Digital Content

Lin JJ, Cardarella S, Lydon CA, Dahlberg SE, Jackman DM, Jänne PA, Johnson BE. Predictors of 5-year survival in EGFR-mutant metastatic lung adenocarcinoma treated with EGFR-TKIs.

Supplemental Methods

CRIS and TOBACCO Databases

Study population

Literature review

Supplemental Figure. Patient flow in the study.

Supplemental Table. Literature series: long-term survivors, advanced NSCLC.

Methods

CRIS and TOBACCO databases

Baseline patient characteristics prospectively collected in the Clinical Research Information System (CRIS) database included: the patient’s date of birth, country of birth, race, Hispanic descent (yes or no), Ashkenazi descent (yes or no), religion, contact information, living environment, medical history, smoking history, date of tumor diagnosis, tumor site/location, histopathology, staging, metastatic site(s) and date(s) of metastasis, any procedural information (including the specific procedure, date and location, and site with laterality), treatment history (specific chemotherapy and dates of treatment), and radiation history. For the Thoracic Oncology Brief Assessment of Cancer and Clinical Outcomes (TOBACCO) database, the following characteristics were prospectively collected: race, smoking status and pack-year history, other exposures (pipe, cigar, asbestos, radium), date of tumor diagnosis, stage at diagnosis, histopathology, date of death, type and date of recurrence if any, date of metastatic or advanced disease, presence and date of brain metastasis, genotype information including the specimen genotyped and mutations identified (on EGFR, KRAS, ALK, BRAF, PIK3CA, HER2, ROS, RET, MET), and treatment history including the type (surgery, chemotherapy, or radiation) and dates.

Study population

A total of 942 patients were identified who had metastatic lung adenocarcinoma within our study time frame. Of these, 668 patients (71%) were tested for EGFR mutation, and 248 patients (37.1% of those tested) were found to have an EGFR mutation. Of these 248 patients, 60 patients were excluded from this analysis as they had been treated at our partner institution, Massachusetts General Hospital Cancer Center, rather than at DFCI, but enrolled in our databases for other research purposes. Subsequently, 49 patients were excluded because of non-sensitizing EGFR mutations (n = 23; including exon 20 insertions, exon 20 deletion c.2284-5_2290del, exon 19 point mutation 2239T>C and 2240T>C, exon 22 mutation 2654C>T, exon 21 mutation 2504A>T and 2497T>G, exon 20 mutation 2303G>T, and exon 19 insertion 2217_2234dup); diagnosis prior to the date cut-off on further review (n = 2); presence of a concurrent malignancy potentially affecting clinical outcome (n = 3); no documented exposure to TKI or chemotherapy (n = 5); seen only once in consultation or incomplete medical records (n = 15); or missing identifier (n = 1). Two more patients were subsequently excluded as their survival times were censored at roughly 22 and 45 months, failing to meet the requirement for a minimum 5-year follow-up among patients still alive at the time of analysis. Ultimately, 137 patients were included. The patients provided written informed consent for the collection of their baseline clinical parameters, outcome, and collection and analysis of the tumor specimens.

Literature review

A literature review was performed using a PubMed search with keywords “long-term survival” and “advanced NSCLC,” revealing a total of 61 entries (as of April 18, 2015). PubMed search was then repeated for keywords “long-term survivors” and “NSCLC,” revealing a total of 53 entries. Reviews and editorials were excluded unless they included new data. Articles had to be published in English. Studies published prior to 2000 (and containing data on patients treated prior to 1990) were excluded. This resulted in 8 published manuscripts, from which the relevant information—including the definition of long-term survival, proportion of long-term survivors, proportion of 5-year survivors (if available), and patient denominator—was extracted, analyzed.

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Figure. Patient flow in this retrospective study, from screening to the EGFR mutation identification and exclusion criteria.

Table

Table. Literature series on long-term survivors with advanced NSCLC.
Study (Year)citation / LTS / N / n (%) LTS / n (%) 5-Yr Survivors / Stage NSCLCa / Treatment Type / n (%) on EGFR-TKI / Treatment Period
Chen et al. (2014)1 / ≥3 yrs / 206 / 28 (13.6%) / Not reported / Advanced / Chemo, CM, TKI / 96 (46.6%) / 4/1999-7/2013
Nishino et al. (2013)2 / ≥5 yrs / 335 / 28 (8.4%) / 28 (8.4%) / Advanced / Gefitinib / 335 (100%) / 7/2002 - not reported
Van Damme et al. (2013)3 / >2 yrs / N/Ab / 31 (N/Ab) / 8 (N/Ab) / IV / Chemo, TKI / Not reported / 3/2009-8/2009
Ozkaya et al. (2012)4 / >5 yrs / 141 / 4 (2.8%) / 4 (2.8%) / IV / Chemo / 0 (0%) / 1/2001-9/2004
Giroux Leprieur et al. (2012)5 / ≥2 yrs / 245 / 39 (15.9%) / 1 (0.4%) / IV / Chemo, TKI / 13 (5.3%) / 1/2003-12/2006
Kaira et al. (2010)6 / ≥5 yrs / 124 / 10 (8.1%) / 10 (8.1%) / Advanced / Chemo, TKI / 64 (51.6%) / 9/2002-10/2003
Satoh et al. (2007)7 / >2 yrs / 109 / 14 (12.8%) / 0 (0%) / IV / Chemo, TKI / 13 (11.9%) / 3/1998 - 3/2007
Okamoto et al. (2005)8 / ≥2 yrs / 222 / 17 (7.7%) / 3 (1.4%) / IV / Chemo / 0 (0%) / 1/1990-12/1999
All above datac / 1176 / 46 (3.9%)
Current study / ≥5 yrs / 137 / 20 (14.6%) / 20 (14.6%)
Abbreviations: LTS, long-term survival; yr, year; chemo, chemotherapy; CM, Chinese medicine; TKI, epidermal growth factor receptor-tyrosine kinase inhibitor. a American Joint Committee on Cancer (AJCC) Staging System, 7th edition. b This study did not report on the denominator or the number of total patients from which the 31 LTS patients were derived. c Includes data from all studies above except for Chen et al. (which did not report the number of 5-year survivors) and Van Damme et al. (which did not report the total denominator).
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  3. Van Damme V, Govaerts E, Nackaerts K, et al. Clinical factors predictive of long-term survival in advanced non-small cell lung cancer. Lung Cancer. 2013;79:73-76.
  4. Ozkaya S, Findik S, Dirican A, et al. Long-term survival rates of patients with stage IIIB and IV non-small cell lung cancer treated with cisplatin plus vinorelbine or gemcitabine. Exp Ther Med. 2012;4:1035-1038.
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  8. Okamoto T, Maruyama R, Shoji F, et al. Long-term survivors in stage IV non-small cell lung cancer. Lung cancer. 2005;47:85-91.

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