Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

N. Yamamoto



Author of

  • +

    MO07 - NSCLC - Targeted Therapies II (ID 114)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MO07.13 - Efficacy of afatinib vs. chemotherapy in treatment-naïve patients with non-small cell lung cancer (NSCLC) harbouring activating EGFR mutations with or without metastatic brain disease (ID 1923)

      17:25 - 17:30  |  Author(s): N. Yamamoto

      • Abstract
      • Presentation
      • Slides

      Background
      Afatinib, an irreversible ErbB Family Blocker, was superior to pemetrexed/cisplatin in previously untreated patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in a global Phase III trial, LUX-Lung 3. In patients with the two most common EGFR mutations (Del19, L858R) median progression-free survival (PFS) was 13.6 vs. 6.9 months (HR=0.47, 95% CI: 0.34–0.65; p<0.0001). Here we present the results for subgroups of patients with or without brain metastases (BM) with NSCLC harbouring common EGFR mutations.

      Methods
      In LUX-Lung 3 EGFR mutation-positive patients were randomized 2:1 to afatinib 40 mg daily or up to 6 cycles of pemetrexed/cisplatin at standard doses. Patients with stable BM (asymptomatic, stable >4 weeks with no treatment required) were allowed. Presence of BM was documented by the investigator during screening. Tumour assessments were performed every 6 weeks until 48 weeks and every 12 weeks thereafter until progression, and reviewed independently and by the investigator.

      Results
      308 patients with common EGFR mutations were randomized (afatinib: 204, pemetrexed/cisplatin: 104), including 35 with baseline BM (afatinib: 20, pemetrexed/cisplatin: 15). Of these, Del19 mutation was detected in 11 (afatinib) and 8 (pemetrexed/cisplatin) patients and L858R in 9 (afatinib) and 7 (pemetrexed/cisplatin) patients. The baseline characteristics of patients with or without BM were comparable (females: 74% vs. 66%, median age: 61 vs. 62 years, ECOG 0: 31% vs. 41%, median time since diagnosis: 1.2 vs. 1.1 months, respectively). Within the BM group, baseline characteristics were balanced between treatment arms with the exception of ECOG 1; 80% of afatinib-treated patients had ECOG 1 compared with 53% of those treated with pemetrexed/cisplatin. Median PFS by independent review was 13.7 (afatinib) vs. 8.1 (pemetrexed/cisplatin) months in patients without BM (HR=0.47, 95% CI: 0.33–0.68; p<0.0001), and 11.1 (afatinib) vs. 5.4 (pemetrexed/cisplatin) months in patients with BM (HR=0.52, 95% CI: 0.22–1.23; p=0.13). Objective response in patients without BM was 59% (afatinib) vs. 23% (pemetrexed/cisplatin), odds ratio=4.8, p<0.0001, and 70% (afatinib) vs. 20% (pemetrexed/cisplatin), odds ratio=11.0, p=0.007, in patients with BM. Investigator review showed a median PFS of 13.6 (afatinib) vs. 6.9 (pemetrexed/cisplatin) months in patients without BM (HR=0.38, 95% CI: 0.27–0.53; p<0.0001), and 6.7 (afatinib) vs. 5.4 (pemetrexed/cisplatin) months in those with BM (HR=0.67, 95% CI: 0.29–1.57; p=0.36). By investigator review, progressive disease in the brain was observed for 4.2% (7/167) and 3.7% (3/82) of patients without BM at baseline for afatinib and pemetrexed/cisplatin, respectively. All but one of these patients (on afatinib) had intracranial progression only. The median (range) time to progression in the brain in this small group was 11.6 (1.3, 20.2) months (afatinib) and 5.5 (2.6, 8.2) months (pemetrexed/cisplatin).

      Conclusion
      In patients with previously untreated NSCLC harbouring common EGFR mutations afatinib remains efficacious regardless of the presence or absence of BM. Control of synchronous asymptomatic BM with afatinib compares favourably with existing data for cranial radiation therapy.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MO13 - SCLC I (ID 118)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MO13.08 - A pilot study of adjuvant chemotherapy with irinotecan and cisplatin for completely resected high grade pulmonary neuroendocrine carcinona (Large cell neuroendocrine carcinoma and small cell lung cancer) (ID 1562)

      11:15 - 11:20  |  Author(s): N. Yamamoto

      • Abstract
      • Presentation
      • Slides

      Background
      Large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are recognized as high grade neuroendocrine carcinoma (HGNEC) of the lung. In patients with completely resected HGNEC, platinum-based adjuvant chemotherapy may be considered. However, the optimum chemotherapy regimen has not been determined. We conducted a multicenter single-arm phase II trial to evaluate irinotecan and cisplatin in postoperative adjuvant chemotherapy for HGNEC patients.

      Methods
      Patients with completely resected stage I- IIIA HGNEC received 4 cycles of irinotecan (60 mg/m[2], day 1, 8, 15) plus cisplatin (60 mg/m[2], day 1). This regimen was repeated every 4 weeks. Other eligibility criteria included ECOG PS 0–1, age 20, and <75 years old, adequate organ function, and no prior chemotherapy or radiotherapy. Patients with UGT1A1 polymorphisms (homozygous for *6 or *28, or simultaneously heterozygous *6 and *28), associated with irinotecan-related severe toxicity, were excluded. The primary endpoint was the rate of completion of chemotherapy (defined as underwent 3 or 4 cycles), and secondary endpoints were 3-year relapse free survival (RFS), rate of 3-year survival and toxicities.

      Results
      Forty patients were enrolled between September 2007 and April 2010. Patients’ characteristics were as follows: median age (range) 65 (45-73) years; male 85%; ECOG-PS 1 60%; LCNEC 57% and SCLC 43%; stage IA/IB/IIB/IIIA 32/35/8/5%; 95% received lobectomy. The rate of completion of chemotherapy was 83% (90% C.I.; 71-90%). The rate of overall survival at 3 years was estimated at 81%, and of RFS at 3 years was 74%. The rates of overall survival and RFS at 3 years were 86% and 74% among 23 LCNEC patients, and 74%, 76% among 17 SCLC patients, respectively. Nineteen patients (48%) experienced grade 3 or 4 neutrophils, but only five patients (13%) developed febrile neutropenia. Two patients (5%) developed grade 3 diarrhea, and 4 patients (10%) had grade 3 nausea. No treatment related deaths were observed in this study. All 40 specimens were also diagnosed as HGNEC at pathological central review among 7 pathologists. There were two specimens that showed the difference in between institutional diagnosis and central pathological diagnosis.

      Conclusion
      The combination of irinotecan and cisplatin as postoperative adjuvant chemotherapy was feasible and possibly efficacious for resected HGNEC.In Japan, a randomized phase III trial is ongoing to evaluate adjuvant chemotherapy of irinotecan and cisplatin, compared with etoposide and cisplatin, for completely resected HGNEC.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MO24 - NSCLC - Chemotherapy III (ID 110)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MO24.11 - A prospective multicenter observational study of chemotherapy induced nausea and vomiting in lung cancer patients (ID 862)

      11:30 - 11:35  |  Author(s): N. Yamamoto

      • Abstract
      • Presentation
      • Slides

      Background
      Chemotherapy-induced nausea and vomiting (CINV) is one of the major causes to deteriorate patient’s quality of life. Therefore, it is important to assess the current status of CINV nationwide for the appropriate treatment method to manage CINV. For this purpose, prospective multi-center observational study was performed in Japan.

      Methods
      Between 2011/Apr and 2012/Dec, 458 lung cancer patients who underwent systemic chemotherapy with high (HEC) or moderate emetogenic agents (MEC) were registered and the data in 429 patients were analyzed. CINV status was assessed in acute phase (within 24 hours from chemotherapy start) and late phase (after 24 hours) separately. Multivariate analysis was performed to clear the predictive factors in patient background for CINV.

      Results
      Patient background was as follows; median age 65, 318 male and 111 female patients, 190 patients treated with HEC and 239 with MEC. In acute phase, nausea and vomiting were observed in 5.6% (HEC 6.8%, MEC 4.6%) and 1.2 % (HEC 0.5%, MEC 1.7%) of all patients, respectively. In late phase, nausea and vomiting were observed in 40.1% (HEC 46.3%, MEC 35.2%) and 9.6 % (HEC 7.9%, MEC 10.9%) of all patients, respectively. The frequency of nausea in late phase is significantly higher in HEC than that in MEC. The predictive factors for nausea were a younger age in female patients, and younger age, no drinking history, decreased hemoglobin in male patients. The prediction of CINV by physician was relatively poor in late phase vomiting.

      Conclusion
      In this study, the current status of CINV and antiemetic therapy in lung cancer patients in Japan were elucidated. CINV was frequently observed in late phase and the appropriate management for late emesis is needed according to the guideline.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    O03 - NSCLC - Targeted Therapies I (ID 113)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      O03.05 - Activity of afatinib in uncommon epidermal growth factor receptor (EGFR) mutations: Findings from three trials of afatinib in EGFR mutation-positive lung cancer (ID 1114)

      11:15 - 11:25  |  Author(s): N. Yamamoto

      • Abstract
      • Presentation
      • Slides

      Background
      EGFR (ErbB1) mutations define a lung cancer subtype with exquisite sensitivity to EGFR tyrosine kinase inhibitors (TKIs). While in-frame deletion in exon 19 (Del19) and a point mutation (L858R) in exon 21 are the two most common sensitizing EGFR mutations in non-small cell lung cancer (NSCLC), approximately 10% of EGFR mutation-positive tumours harbour uncommon mutations. These mutations represent a heterogeneous group of rare molecular alterations (or combinations) within exons 18–21, whose oncogenicity and sensitivity to EGFR TKIs may vary and has not been prospectively studied. Here we present the first prospective data series on activity of afatinib, the irreversible ErbB Family Blocker, in patients with tumours harbouring uncommon EGFR mutations.

      Methods
      This analysis is based on data from EGFR mutation-positive patients included in the LUX-Lung 2 (Phase II), LUX-Lung 3 and LUX-Lung 6 (both Phase III) studies. EGFR mutations were identified prospectively by direct sequencing in LUX-Lung 2 and by central testing with TheraScreen EGFR RGQ PCR kit (TheraScreen29) in LUX-Lung 3 and 6. Patients were classified as having common (Del19 or L858R) or uncommon (all other single or complex) mutations. Uncommon mutations were categorized into three groups: de novo T790M (alone or in combination with other mutations); exon 20 insertions; and other. Objective response rate (ORR), disease control (DCR), duration of response and progression-free survival (PFS) were assessed by independent review.

      Results
      Seventy-five patients (LUX-Lung 2: n=23; LUX-Lung 3: n=26; and LUX-Lung 6: n=26) had uncommon mutations, accounting for 12.5% of all afatinib patients in these studies. The majority of patients received afatinib first line; 13 patients from LUX-Lung 2 received afatinib after chemotherapy. Breakdown into the three groups was T790M: n=14; Exon 20 insertions: n=23; other: n=38 (most frequent types were L861Q: n=12; G719X: n=8; G719X+S768I: n= 5; G719X+L861Q: n=3). Efficacy results for each group are shown below. Further details by mutation status will be presented.

      Mutation ORR, % (n=) Median duration of response, months (95% confidence interval) DCR (ORR + stable disease), % (n) Median PFS, months (95% confidence interval) Median survival, months (95% confidence interval)
      De novo T790M alone or in combination with other mutations (n=14) 14.3 (2) Individual response durations: 4.1, 12.4 64.2 (9) 2.9 (1.2−8.3) 14.9 (8.1−24.9)
      Exon 20 insertions (n=23) 8.7 (2) Individual response durations: 4.2, 10.1 65.2 (15) 2.7 (1.8−4.2) 9.4 (4.1−21.0)
      Other (n=38) 71.1 (27) 11.1 (4.1, 15.2) 84.2 (32) 10.7 (5.6−14.7) 18.6 (16.4−not estimable)

      Conclusion
      Afatinib was active in lung tumours harbouring uncommon EGFR mutations, such as G719X, L861Q, S768I. Rate and duration of response was comparable with that previously observed in patients with common mutations in these trials. The response rate was low in tumours with de novo T790M mutations and insertions in exon 20 but durable tumour control was achieved in some patients. To date this is the largest analysis of data for prospectively identified patients with uncommon EGFR mutations; treatment options in this heterogeneous group of tumours will be discussed.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      P1.10-020 - Dose adjustment of single agent amrubicin in lung cancer patients with impaired hepatic function (ID 1348)

      09:30 - 09:30  |  Author(s): N. Yamamoto

      • Abstract

      Background
      The pharmacokinetics (PK) of amrubicin (AMR) in lung cancer patients with impaired hepatic function have not been reported. The objectives of this study were to evaluate the PK of AMR and its major metabolite, amrubicinol (AMR-OH), in lung cancer patients with or without impaired hepatic function, and to assess the validity of dose adjustment of AMR based on hepatic function.

      Methods
      Eligibility criteria included the presence of histologically or cytologically proven lung cancer, an ECOG PS of 0 to 2, age 20 to 70 years old, and no evidence of hepatitis B virus infection. The dose was adjusted from 25 to 45 mg/m[2]/day (iv, days 1-3, q3w) based on the history of prior treatment and baseline values of total bilirubin (T-bil), AST and ALT (Table 1). Figure 1

      Results
      Five patients with impaired hepatic function (arm I) and 10 patients with normal hepatic function (arm N) were enrolled. Terminal half-life (t~1/2~) and clearance of AMR in plasma, and t~1/2~ of AMR-OH in blood did not differ between the two arms. Area under the curve (AUC~0-24~) of AMR in plasma and AUC~0-120~ of AMR-OH in blood in arm I were similar or lower compared to those in arm N (Table 2). The dose-adjusted AUCs of AMR and AMR-OH did not show a tendency to increase with increases in baseline T-bil, AST and ALT. Two deaths occurred in arm I (one due to disease progression, and the other due to an unspecified reason), but the toxicities in arm I were not severe compared with those in arm N. Figure 1

      Conclusion
      These data show the validity of dose adjustment of AMR in patients with impaired hepatic function.

  • +

    P2.09 - Poster Session 2 - Combined Modality (ID 213)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
    • +

      P2.09-006 - Long-term results of a phase II trial of S-1 and cisplatin with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer (ID 1371)

      09:30 - 09:30  |  Author(s): N. Yamamoto

      • Abstract

      Background
      Concurrent chemoradiotherapy is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). S-1 has been shown to be significant efficacious for treating advanced NSCLC. Our previous phase II study reported short-term outcomes of cisplatin (CDDP)/S-1 chemoradiotherapy. Because CDDP/S-1 chemoradiotherapy is considered to have advantages over others in overall survival (OS) and toxicity, we analyzed its long-term outcomes by following up patients included in the phase II study.

      Methods
      Forty-eight patients (aged <75 years) with unresectable stage III NSCLC were evaluated. They were treated with CDDP (60 mg/m[2] on day 1) intravenously and oral S-1 (40 mg/m[2] twice daily on days 1–14); this regimen was repeated every 4 weeks for four cycles. A 60-Gy thoracic radiation dose was delivered in 30 fractions beginning on day 2.

      Results
      After a median follow-up of 6.3 years (range, 5.7–7.4 years), the median OS was 2.8 years [95% confidence interval (CI); 1.04–4.63 years], and the 3- and 5-year OS rates were 49.7% (95% CI: 35.6%–63.8%) and 33.0% (95% CI: 20.0%–46.6%), respectively. Out of the several variables evaluated as predictors of OS, including gender, age, stage, histology, and performance status (PS), only PS proved to be a statistically significant predictor in both univariate and multivariate analyses.

      Conclusion
      CDDP/S-1 concurrent thoracic radiotherapy is clinically feasible and highly efficacious. Despite our relatively small sample size, the benefits of this regimen revealed in this study warrant further research.

  • +

    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
    • +

      P3.06-012 - Pharmacogenetic study of Japanese patients with advanced non-squamous non-small cell lung cancer treated with pemetrexed plus cisplatin (ID 1407)

      09:30 - 09:30  |  Author(s): N. Yamamoto

      • Abstract

      Background
      Pemetrexed (PEM) inhibits multiple enzymes in the folate (F) pathway. Several studies show that genetic polymorphisms in these enzymes influence the efficacy and toxicity of PEM. We aimed to investigate the relationship between genetic polymorphisms associated with the F pathway and clinical outcomes of Japanese patients with advanced non-squamous non-small cell lung cancer (NSQ-NSCLC) treated with PEM plus cisplatin (CIS).

      Methods
      We analyzed 34 polymorphisms in 14 genes associated with the F pathway in NSQ-NSCLC patients treated with PEM plus CIS: ABCC11, ADA, ATIC, DHFR, ERCC1, FPGS, GGH, MTHFD1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, and TYMS. These polymorphisms were compared with clinical outcomes such as response, toxicity, and progression-free survival (PFS) using Pearson’s χ[2] test and the log-rank test.

      Results
      All 56 patients were Japanese, with a median age of 62 years; 57.1% were male, 96.4% had an Eastern Cooperative Oncology Group Performance Status of 0–1, 96.4% had stage IV disease, and 94.6% had adenocarcinoma. The response rate, disease control rate, and median PFS were 32.2%, 78.6%, and 4.7 months, respectively. Of the 38 polymorphisms tested, none were associated with response or toxicity, but 2 single nucleotide polymorphisms (SNPs) (in the gamma-glutamyl hydrolase [GGH 452C>T] and methionine synthase [MTR 2756A>G] genes) were significantly associated with PFS. Patients harboring the GGH-C452C variant had significantly longer PFS (5.6 vs 2.8 months; p < 0.0001) than those with the C452T or T452T variants. Further, patients harboring the MTR-A2756A variant had significantly longer PFS (5.3 vs 3.7 months; p = 0.036) than those with the A2756G variant. In addition, among patients with the GGH-C452C variant, those harboring the MTR-A2756A variant had significantly longer PFS (5.9 vs 4.3 months; p = 0.044) than those with the A2756G variant.

      Conclusion
      SNPs in GGH and MTR seem to predict differences in PFS in NSQ-NSCLC patients treated with PEM plus CIS, and a combination of these 2 SNPs may predict differences in PFS more accurately. These results should be validated in larger, adequately designed prospective studies.

  • +

    P3.09 - Poster Session 3 - Combined Modality (ID 214)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
    • +

      P3.09-003 - Phase II study of nimotuzumab in combination with concurrent chemoradiotherapy (CRT) in patients with locally advanced non-small cell lung cancer (NSCLC). (ID 707)

      09:30 - 09:30  |  Author(s): N. Yamamoto

      • Abstract

      Background
      Nimotuzumab, a humanized IgG~1~ monoclonal anti-EGFR antibody, is approved and widely used in patients (pts) with head and neck cancer or malignant glioma in combination with radiotherapy (RT) in several countries. In previous clinical studies, nimotuzumab has demonstrated a very mild and low incidence of skin toxicity compared to other anti-EGFR antibodies. On in-vitro and in-vivo experiments using NSCLC cell lines, nimotuzumab showed a radio-sensitizing effect.

      Methods
      This open-label, multicenter phase II study evaluated the tolerability and efficacy of nimotuzumab in combination with concurrent CRT in pts with unresectable locally advanced NSCLC. All eligible pts received concurrent thoracic RT (60 Gy, 2 Gy/day, 6 weeks from day 1) and 4 cycles of chemotherapy (cisplatin 80 mg/m[2] on day 1, vinorelbine 20 mg/m[2] on days 1 and 8) once every 4 weeks as scheduled. Nimotuzumab (200 mg) was administrated once a week from cycle 1 to 4. The primary endpoint was tolerability in combination with concurrent CRT, which was measured by the percentage of pts who completed 60 Gy of RT within 8 weeks, completed 2 cycles of chemotherapy and received more than 75% of nimotuzumab.

      Results
      Between June 2009 and May 2010, 40 pts were enrolled from 7 institutions in Japan, and 39 eligible pts received the study treatment. The pts characteristics (n = 39) were as follows: 62 years (median); male/female, 34/5; stage IIIA/B, 21/18; PS0/1, 25/14. Thirty-four pts (87%) met the criteria for treatment tolerability, and 38 pts (97%) completed 60 Gy of RT within 8 weeks. Infusion reaction, >grade 3 skin rash, >grade 3 radiation pneumonitis, or >grade 4 nonhematological toxicity were not observed. The 2-year overall survival rate for the 39 pts was 76% (95% CI; 59-87%). The median PFS was 16.7 months; and 30 pts were alive at the cutoff date (Nov 2011). The 1-year PFS rate for pts with squamous cell carcinoma (Sq; n = 16) was 75%, while that for pts with non-squamous cell carcinoma (non-Sq; n = 23) was 41%. In terms of the first relapse site, in-field relapse rates were low for both Sq (3/16; 19%) and non-Sq (3/23; 13%). However, the distant relapse rate was significantly higher for non-Sq (15/23; 65%) than that for Sq (2/16; 13%) (p<0.01, chi-square test with Yates correction).

      Conclusion
      Addition of nimotuzumab to the concurrent CRT in this setting was well tolerated with clinical benefit to the patients. The low in field relapse rates may be attributed to the radio-sensitizing effect of nimotuzumab. These findings warrant further clinical evaluation of nimotuzumab/cisplatin/vinorelbine/RT in a phase III trial.

  • +

    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      P3.11-023 - Comparative safety profile of afatinib in Asian and non-Asian patients with EGFR mutation-positive (EGFR M+) non-small cell lung cancer (NSCLC) (ID 2141)

      09:30 - 09:30  |  Author(s): N. Yamamoto

      • Abstract

      Background
      Afatinib is an oral, irreversible ErbB Family Blocker which showed superior efficacy to standard first-line chemotherapy in two large randomized Phase III trials in global (LUX-Lung 3) and Asian (LUX-Lung 6) EGFR M+ patients. In both trials, median progression-free survival on afatinib was 11 months by independent review. This was also reflected in median treatment duration of 11–12 months in both trials. With long-term treatment duration, the safety profile of afatinib becomes particularly relevant to patients and physicians, and needs to be well characterized. Furthermore, differences in the pattern of some adverse events (AEs; notably interstitial lung disease [ILD]) have been previously described in Asian and non-Asian patients with reversible EGFR tyrosine kinase inhibitors. Here, we present a detailed review of afatinib’s safety profile in Asian and non-Asian patients.

      Methods
      229 (LUX-Lung 3) and 239 (LUX-Lung 6) EGFR M+ patients were treated with afatinib 40mg daily until progression or intolerable AEs. Afatinib dose could be escalated to 50mg daily or reduced to 30mg or 20mg based on predefined study criteria. Patients from both trials were grouped according to ethnicity: Asian vs. non-Asian. On-treatment AEs were summarized by preferred/grouped terms and graded using NCI-CTCAEv3.0.

      Results
      404 Asian (66% China/Taiwan; 16% Southeast Asia; 13% Japan; 5% Korea) and 64 non-Asian patients (95% Caucasian; 3% American-Indian; 2% African-American) received afatinib, with median exposure of 359 and 261 days, respectively. There was no difference in afatinib pharmacokinetic exposure in Asian vs. non-Asian patients. All patients reported at least one AE. Most common AEs were EGFR-mediated and are summarized in the table. Figure 1 Drug-related AEs leading to discontinuation were slightly higher in Asian patients, but at a rate lower than with chemotherapy (28%). Related ILD-like events occurred in four Asian patients (three Grade ≥3) and no non-Asian patients.

      Conclusion
      Most common drug-related AEs with afatinib were EGFR mediated and occurred at similar frequency in Asian and non-Asian patients. Treatment discontinuation due to EGFR-related AEs was low in both groups, indicating that afatinib has a manageable safety profile in both populations and is suitable for long-term treatment of EGFR M+ NSCLC patients.