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H. Sakai



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    O15 - NSCLC - Chemotherapy II (ID 109)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O15.05 - Randomized Phase III Trial of S-1 plus Cisplatin versus Docetaxel plus Cisplatin for Advanced Non-Small-Cell Lung Cancer (TCOG0701): Subgroup Analysis. (ID 1895)

      11:15 - 11:25  |  Author(s): H. Sakai

      • Abstract
      • Presentation
      • Slides

      Background
      Docetaxel plus cisplatin (DP) is the only third-generation regimen that has demonstrated statistically significant improvements in overall survival and QOL by head-to-head comparison with a second-generation regimen (vindesine plus cisplatin) in patients with advanced non-small cell lung cancer (NSCLC). S-1 plus cisplatin (SP) has shown activity and good tolerability in phase II settings. Molecularly targeted agents including bevacizumab (BEV) have shown activity and safety in non-squamous (non-Sq) NSCLC.

      Methods
      Patients with previously untreated stage IIIB or IV NSCLC, an ECOG PS of 0-1 and adequate organ functions were randomly assigned to receive either oral S-1 80 mg/m[2]/day (40 mg/m[2] b.i.d.) on days 1 to 21 plus cisplatin 60 mg/m[2] on day 8 every 5 weeks or docetaxel 60 mg/m[2 ]on day 1 plus cisplatin 80 mg/m[2] on day 1 every 3 weeks, both up to 6 cycles. The primary endpoint was overall survival (OS). A non-inferiority study design was employed; the upper confidence interval (CI) limit of the hazard ratio (HR) was <1.322. Secondary endpoints included progression-free survival (PFS), response, safety, and QOL. Subgroup analysis by histology (non-Sq vs Sq) was conducted.

      Results
      From April 2007 through December 2008, 608 patients were randomly assigned to SP (n=303) or DP (n=305) at 66 sites in Japan. Patient demographics were well balanced between the two groups. Non-Sq and Sq patients in SP/DP arm was 251/247 and 50/48 respectively. Two interim analyses were preplanned. At the final analysis, a total of 480 deaths had occurred. The primary endpoint was met. OS in the SP arm was non-inferior to that in the DP arm (median survival, 16.1 vs. 17.1 months, respectively; HR=1.013; 96.4% confidence interval, 0.837-1.227). PFS was 4.9 months in the SP arm and 5.2 months in the DP arm. The rates of febrile neutropenia (7.4% vs. 1.0%), grade 3/4 neutropenia (73.4% vs. 22.9%), grade 3/4 infection (14.5% vs. 5.3%), and grade 1/2 alopecia (59.3% vs. 12.3%) were significantly lower in the SP arm than in the DP arm. In terms of physical functioning and global functioning on the EORTC QLQ-C30 and lung cancer module (LC-13), QOL was better in the SP arm (repeated measures ANOVA: p<0.01). Subgroup analysis by histology revealed that the median OS of non-Sq and Sq patients in SP/DP group was 17.4/19.1 months and 12.3/11.7 months respectively, of which hazard ratio was 0.973 (95% CI, 0.797-1.187) and 1.239 (95% CI, 0.819-1.874). Interaction P value was 0.3004.

      Conclusion
      S-1 plus cisplatin is a standard first-line chemotherapeutic regimen for advanced NSCLC both non-Sq and Sq histology. Favorable toxicity profile of the SP regimen and encouraging outcome in patients with non-Sq prompted us to conduct a prospective study of SP plus BEV and maintenance S-1 BEV for non-SQ currently underway.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-018 - nab-Paclitaxel in combination with carboplatin as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC): analysis of peripheral neuropathy (ID 1022)

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

      • Abstract

      Background
      Peripheral neuropathy (PN) is a common side effect associated with taxane treatment. In a phase III trial, nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C) vs solvent-based paclitaxel (sb-P) + C significantly improved ORR (primary endpoint; 33% vs 25%; P = 0.005), with a trend toward improved OS and PFS in patients with advanced NSCLC. Here, we report on the PN profile of nab-P/C vs sb-P/C.

      Methods
      Patients with untreated stage IIIB/IV NSCLC were randomized 1:1 to nab-P 100 mg/m[2] on d 1, 8, 15 or sb-P 200 mg/m[2] q 1 q21d; both arms received C AUC 6 day 1 q21d. PN was assessed by Standardized MedDRA Query (SMQ) for neuropathy (broad scope) unless otherwise indicated. Patient-reported taxane-related neuropathy symptoms were assessed by the Functional Assessment of Cancer Therapy (FACT)-Taxane Additional Concerns scale.

      Results
      nab-P/C was associated with significantly less PN vs sb-P/C (all grade: 46% vs 62%; P < 0.001) and grade 3/4 treatment-related PN (3% vs 12%; P < 0.001). Grade 4 PN occurred in 2 patients in the sb-P/C arm vs 0 patients in the nab-P/C arm. PN led to taxane dose reductions in 2% vs 7% and delays in 3% vs 8% of patients in the nab-P/C vs sb-P/C arm. Physician assessment of PN based on NCI CTCAE grade showed fewer instances of worsening with nab-P/C vs sb-P/C. At baseline, ≥ 95% of patients in both arms were assessed with grade 0 PN, but at final evaluation, significant treatment differences favoring the nab-P/C arm were observed, with fewer nab-P/C−treated patients shifting from grade 0 to grades 1-4 (38%) relative to the sb-P/C arm (58%; P < 0.001). Fewer patients receiving ≤ 6 cycles (median number of cycles = 6) in the nab-P/C vs sb-P/C arms experienced all-grade PN (41% vs 60%); 2% vs 10% of these patients experienced grade 3/4 PN (no patients in the nab-P/C arm experienced grade 4 PN). Median time to PN onset of any grade was longer with nab-P/C vs sb-P/C, 49 vs 38 days (P < 0.001); grade 2-4, 105 vs 78 days (P = 0.04) and grade 3/4, 121 vs 106 days (P = 0.723). The median time to improvement of grade 3/4 PN to grade 1 was 38 vs 104 days (P = 0.326) with nab-P/C vs sb-P/C. Patient-reported FACT-Taxane PN subscore at final evaluation also demonstrated a statistically significant treatment effect favoring nab-P/C (P < 0.001). Most patients completed the FACT-Taxane questionnaire at baseline (98%) and provided follow-up assessments (94%) at each cycle. Deterioration in patient-reported PN subscore at or after the development of grade 3/4 PN was lower for nab-P/C vs sb-P/C (median change from baseline 4.5 vs 10).

      Conclusion
      In this trial, nab-P/C was associated with lower rates PN compared with sb-P/C. PN occurred later during treatment with nab-P/C vs sb-P/C, and the majority of patients experienced improvement of PN symptoms within approximately 1 month. Patients receiving ≤ 6 cycles of therapy with nab-P/C had less PN compared with those receiving sb-P/C.