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H. Saka



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    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
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      P2.10-026 - Final results of EGFR mutation reanalysis and KRAS mutation screening by Scorpion ARMS method: Phase II Study of Erlotinib for EGFR wild type Non-small cell Lung Cancer Patients. Central Japan Lung Study Group (CJLSG) 0903 trial. (ID 1529)

      09:30 - 09:30  |  Author(s): H. Saka

      • Abstract

      Background
      Erlotinib might benefit non-small cell lung cancer (NSCLC) patients with EGFR wild-type (WT) genotype based on the subgroup analysis of the BR21 trial and SATURN trial. However, the sensitivity of methods for detection of EGFR mutation can influence the evaluation of erlotinib efficacy. We conducted CJLSG0903 trial, a phase II study of erlotinib for previously treated EGFR WT NSCLC patients screened by peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp method. The efficacy and safety results of CJLSG0903 were previously reported at the ESMO meeting 2012. Here we present the final results of EGFR mutation reanalysis and KRAS mutation screening by S-ARMS method.

      Methods
      Stage IIIB or IV NSCLC patients were eligible. EGFR mutation status was screened by PNA-LNA PCR clamp method, which is known to be a highly sensitive. Primary endpoint was objective response rate (ORR). Oral erlotinib 150 mg was given daily until progression or unacceptable toxicity.

      Results
      From February 2010 and April 2012, 53 evaluable patients were enrolled. ORR was 11.3% (95% confidence interval: 4.3–23.0%). We performed preplanned reanalysis of EGFR mutation status and KRAS mutation by Scorpion ARMS (S-ARMS) methods if remaining samples from participants were available. Samples from 26 patients (49%) were available for EGFR mutation reanalysis. Only one patient who achieved partial response (PR) was EGFR mutation positive (exon 19 deletion). In 25 patients, EGFR WT genotype was reconfirmed by S-ARMS method. Two of them achieved PR. ORR was 8.0 % in patient with EGFR WT genotype confirmed by both PNA-LNA PCR clamp and S-ARMS methods. Samples from 42 patients (79%) were available for KRAS mutation screening. KRAS mutations were detected in 4 of 42 patients, and progressive disease (PD) was observed in all of KRAS mutation positive patients.

      Conclusion
      Erlotinib still shows activity in patients with EGFR WT genotype confirmed by two different highly sensitive methods. Activating KRAS mutation might be negative predictive factor for erlotinib efficacy in patients with EGFR WT genotype. (UMIN Clinical Trials Registry: UMIN000002692)

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      P2.10-033 - Phase II study of weekly amrubicin in patients with refractory or relapsed non-small cell lung cancer (ID 2103)

      09:30 - 09:30  |  Author(s): H. Saka

      • Abstract

      Background
      Amrubicin (AMR) is a potent topoisomerase II inhibitor, and promising agent for both small cell and non-small cell lung cancer. AMR is usually administered on days 1-3 of a 21-day course by intravenous infusion. However, it causes severe, occasionally fatal, toxicity of febrile neutropenia. Otherwise, previous trials revealed that a weekly schedule of chemotherapy had a higher dose intensity, less severe adverse effects and anti-tumor activity as effective as other treatments. We conducted a phase I study, and reported the safety and recommended dose in a weekly schedule (60 mg/m[2] weekly on 1st and 8th day with a rest on day 15).

      Methods
      Refractory or relapsed non-small cell lung cancer patients after 1 or 2 regimens, with older than 20 and with adequate main organ functions were eligible. AMR was administered at the dose of 60 mg/m2 weekly (on days 1 and 8 every 3weeks). Primary endpoint was objective response rate. Secondary endpoints were adverse events, progression-free survival, and disease control rate (CR, PR, and SD).

      Results
      Thirty-three patients were enrolled. Twelve were female, 21 were male, and their median age was 67 years (range, 38-80). Twenty-four were adeno- carcinoma, 7 were squamous cell carcinoma, and 2 were non-small cell carcinoma. One hundred twenty-nine courses were given (median: 3, range: 1-20). The objective response rate was 6.0%, and the disease control rate was 51.5%. Median follow-up time was 9.3 months, and median progression-free survival was 2.7 months. Common grade 3/4 adverse events were white blood cell decreased (63.6%), neutrophil count decreased (45.5%), anemia (15.2%), anorexia (15.2%), and fatigue (12.1%). Febrile neutropenia was noted in two patients. There was no treatment-related death.

      Conclusion
      Primary endpoint was not met in this study. However, weekly AMR showed high disease control rate and good tolerability. Weekly AMR is promising in refractory or relapsed non-small cell lung cancer patients.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P3.09-007 - Update data of biomarker analysis of WJOG4107 (A randomized phase II trial of adjuvant chemotherapy with S-1 versus CDDP+S-1 for resected stage II-IIIA non-small cell lung cancer (NSCLC)) (ID 1504)

      09:30 - 09:30  |  Author(s): H. Saka

      • Abstract

      Background
      We conducted a randomized phase II trial for patients with resected stage II-IIIA NSCLC comparing postoperative oral S-1 (80 mg/m2/day for consecutive 2 weeks q3w for 1 year) (S) (N=100) or cisplatin (CDDP) (60 mg/m2 day1) plus oral S-1, (80 mg/m2/day for 2 weeks) q3w for 4 cycles (PS)(N=100). We reported that disease free survival rate at 2 years (DFS@2) (95% confidence interval: CI), a primary endpoint, was 66 (55-74) % for S and 58 (48-67)% for PS. Here, we report the preliminary results of preplanned biomarker analysis, a co-primary endpoint, to identify molecules whose expression is significantly associated with patient outcome.

      Methods
      　cDNA extracted from macro-dissected formalin-fixed paraffin-embedded specimens were available for 197/200 patients. Thirty-one genes including those whose expressions have been potentially associated with　CDDP (e.g. ERCC1, XRCC1, BRCA1, GSTpi, HMG1, TBP) or fluorouracil (FU) sensitivity (TS, DHFR, DPD, UMPS, UPP1) were measured by QGE analysis (MassArray, Sequenom, CA). Additional analysis are being performed to assess ERCC1 isoform expression with an isoform-specific TaqMan probe (Applied Biosystems, CA). The expression of each gene was dichotomized according to its median value.

      Results
      Molecules such as ERCC1 and GSTpi whose expression have been previously associated with CDDP sensitivity did not emerge as predictive markers (P=0.7908, 0.6406, respectively). We quantitated ERCC1 by isotype (202 and 204 cannot be distinguished). There was a trend in patients with high 201 or 202/204, CDDP/S-1 was worse than S-1.

      Conclusion
      Quantitation of ERCC1 by isotype may define a patient subset that would benefit from postoperative platinum therapy.

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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
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      P3.10-006 - Post-progression survival after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations (ID 653)

      09:30 - 09:30  |  Author(s): H. Saka

      • Abstract

      Background
      Non-small cell lung cancer (NSCLC) patients harboring the epidermal growth factor receptor (EGFR) mutation show a survival benefit on treatment with EGFR-tyrosine kinase inhibitor (EGFR-TKI); however, few studies report on post-progression tumor behavior after treatment with EGFR-TKI. We investigated the post-progression clinical course after treatment with EGFR-TKI in NSCLC patients harboring the EGFR mutation. We also evaluated the correlation between the site of relapse after EGFR-TKI treatment and prognosis.

      Methods
      We retrospectively reviewed clinical data of stage IV or recurrent NSCLC patients harboring the EGFR mutation, who received EGFR-TKI as first-line treatment in our institute from 2009 to 2011.

      Results
      Thirty-six patients received EGFR-TKI as first-line therapy. Thirty of these patients with recurrent NSCLC were enrolled in this study. The median age of the patients was76 years (range, 38–97), and the male/female ratio was 4/26. The median progression-free survival (PFS) after EGFR-TKI treatment was 8.2months and the median overall survival (OS) was 20.4months. Sites of relapse in patients with progressive disease (PD) were the brain, pleural effusion, bone, and lung (n=5, 13, 6, and 8, respectively). Twenty-one patients received sequential therapy: 11 patients received continued EGFR-TKI treatment beyond PD and 10 patients received second-line therapy. Second-line therapies were platinum-based doublet therapy, monotherapy, and another cycle of EGFR-TKI (n = 6, 2, and 2 patients, respectively). Post-progression survival (PPS) of all the patients after treatment with EGFR-TKI was 9.2 months, whereas that of patients who received second-line therapy was 14 months. Subgroup analysis according to the site of relapse showed that after first-line EGFR-TKI treatment, PFS tended to be higher for patients with a relapse in the brain (11.6 months) than for patients with sites of relapse other than the brain (8.2 months).

      Conclusion
      PPS of all the patients after treatment with EGFR-TKI was 9.2 months, whereas that of patients who received second-line therapy was 14 months. Subgroup analysis showed that patients with a relapse in the brain might survive longer.

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      P3.10-023 - Phase II study of Pemetrexed + Carboplatin as first line therapy for advanced non-squamous non-small cell lung cancer without EGFR Mutation. : CENTRAL JAPAN LUNG STUDY GROUP (CJLSG) 0906 TRIAL (ID 1511)

      09:30 - 09:30  |  Author(s): H. Saka

      • Abstract

      Background
      In advanced non-squamous non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) status is important to determine the treatment. However, many previous studies of NSCLC were investigated regardless of EGFR mutation status. Therefore, we thought that the trial only for EGFR wild-type (WT) patients (pts) is required. We evaluated the efficacy and safety of combination therapy with pemetrexed (Pem) and carboplatin (Cb) for advanced non-squamous NSCLC EGFR-WT pts.

      Methods
      This study was multicenter, phase II trial. We recruited non-Sq NSCLC patients without EGFR mutation. Eligibility criteria were as follows; stage IIIB or IV, or recurrent disease after surgery (rec), no prior chemotherapy, age 20 to 74, ECOG PS: 0-1, and adequate organ function. We evaluated the efficacy and safety of Pem 500mg/m2 and Cb AUC 6 on day1, every 3 weeks, for 3 to 6 cycles. The primary endpoint was response rate (RR) and secondary endpoints were safety and disease control rate (DCR). We planned the sample size was 48 patients and recruited 54 pts. (Unique trial Number; UMIN000003393)

      Results
      From March 2009 to February 2012, 54 pts were enrolled from 18 centers. Of 53 evaluable for analysis, the median age was 65 years (range, 45–73); 41/12 males/females; 6/44/3 with IIIB/IV/rec; 47/3/3 with adenocarcinoma/large cell carcinoma/NSCLC. The median number of cycles was 4 (range, 1–6). There were 19 partial responses with an RR of 35.8% (95% CI, 23.6–51.0%). SD was observed in 20 pts and DCR was 73.6%. Median PFS was 5.2 months and median OS was 12.months. Major adverse event was grade 3–4 neutropenia in 19 pts (35.8%), anemia in 16 pts (30.2%), thrombocytopenia in 17 pts (32.1%). There was no treatment-related death.

      Conclusion
      Combination chemotherapy with Pem and Cb showed efficacious and well tolerated in advanced non-Sq NSCLC without EGFR mutation. This combination could include one of the options in standard regimen for 1[st] line therapy for advanced non-Sq NSCLC.