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Hiroyuki Sakurai



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    MA06 - Challenges in the Treatment of Early Stage NSCLC (ID 124)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      MA06.06 - A Phase III Study of Adjuvant Chemotherapy in Patients with Completely Resected, Node-Negative Non-Small Cell Lung Cancer  (Now Available) (ID 285)

      13:30 - 15:00  |  Author(s): Hiroyuki Sakurai

      • Abstract
      • Presentation
      • Slides

      Background

      Post-operative UFT (tegafur/uracil) has been shown to prolong survival of Japanese patients with completely resected, p-stage I (T1> 2 cm) non-small cell lung cancer (NSCLC). This trial, the Japan Clinical Oncology Group (JCOG) 0707, aimed at estimating the efficacy of S-1 (tegafur/gimeracil/oteracil) compared to UFT as adjuvant therapy in this population.

      Method

      Eligible patients had received complete resection with lymph node dissection for p-stage I (T1-2N0M0, T1> 2 cm, by 5thEdition UICC TNM) NSCLC, within 56 days of enrollment. Patients were randomized to receive: oral UFT 250mg/m2/day for 2 years (Arm A), or oral S-1 80mg/m2/day for 2 weeks and 1 week rest, for 1 year (Arm B). The initial primary endpoint was overall survival (OS). Based upon the monitoring in Jun. 2013, which showed the combined OS of the 2 arms better than expected (4-year OS of 91.6% vs. presumed 5-year OS of 70-76.5%), it was judged to be underpowered. The study protocol was amended so that the primary endpoint is relapse-free survival (RFS). With the calculated sample size of 960, this study would detect the superiority of Arm B over Arm A with power 80% and one-sided type I error of 0.05, assuming the 5-year RFS of 75% in Arm A and the hazard ratio of 0.75.

      Result

      From Nov. 2008 to Dec. 2013, 963 patients were enrolled (Arm A : 482, Arm B : 481): median age 66 (range: 33 to 80), male 58%, adenocarcinoma 80%, p-T1/T2 46%/54%. Only 2 received pneumonectomy. >Grade 3 toxicities (hematologic/nonhematologic) were observed in 15.9 (1.5/14.7) % in Arm A, and in 14.9 (3.6/12.1) % in Arm B, respectively. 60.0% of the patients in Arm A and 54.7% of them in Arm B completed the protocol treatment (p=0.10). There were 4 cases of deaths during protocol treatment, probably of cardio-vascular origin, with 1 in Arm A and 3 in Arm B. At the data cut-off of Dec. 2018, the hazard ratio (HR, Arm B vs. Arm A) of RFS was 1.06 (95% confidence interval (C.I.): 0.82-1.36), showing no superiority of S-1 over UFT. The HR of OS was 1.10 (95% C.I.: 0.81-1.50). The 5-year RFS/OS rates were 79.4%/88.8% in Arm A and 79.5%/89.7% in Arm B, respectively. Pre-specified subset analyses for gender, age, smoking, stage, tumor side, lymph node dissection area, pleural invasion and histology revealed no remarkable results; S-1 arm was not superior to UFT arm in each analysis. Of the 77 and 85 OS events for Arm A/Arm B, 45 each (58%/53%, respectively) were due to the NSCLC. During the follow-up period, secondary malignancy was observed in 85 (17.8%) and 84 (17.8%) in Arm A and Arm B, respectively.

      Conclusion

      Post-operative adjuvant therapy with oral S-1 was not superior to that with UFT in stage I (T>2 cm) NSCLC after complete resection. UFT remains standard in this population. Future investigation should incorporate identification of high-risk population for recurrence, since survival of each arm was so good with substantial number of OS events due to other causes of deaths in this trial.

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    P1.17 - Treatment of Early Stage/Localized Disease (ID 188)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.17-04 - Multicenter Observational Study of Node-Negative Non-Small Cell Lung Cancer Patients Who Are Excluded from a Clinical Trial (ID 678)

      09:45 - 18:00  |  Presenting Author(s): Hiroyuki Sakurai

      • Abstract

      Background

      The Japan Clinical Oncology Group (JCOG) conducted a randomized phase III trial (JCOG0707), which compared the survival benefit of tegafur/uracil (UFT) and tegafur/gimeracil/oteracil (S-1) for completely resected pathological stage I (T1>2 cm and T2 in the 6th TNM classification) non-small cell lung cancer (NSCLC). A total of 963 patients were enrolled. Recently, there is a growing concern that those who participated in clinical trials are highly selected and do not represent the “real-world” population. Hereby, we conducted a multicenter observational study of patients excluded from JCOG0707 trial during the study period.

      Method

      Patients with completely resected pathological stage I NSCLC, eligible for, but excluded from the JCOG0707 trial during the enrollment period (Nov. 2008– Dec. 2013) were eligible for this study. Physicians from institutions that participated in the JCOG0707 retrospectively assessed the medical records of each patient. The final survival data were collected as of Dec. 2018.

      Result

      Of the 48 institutions participating in JCOG0707, 34 participated in this observational study. They had enrolled 917 (“JCOG” cohort) to JCOG0707. To this study, 5004 patients (“All” cohort), or 85% of those initially considered for JCOG0707 at the 34 institutions, were enrolled. Among them, 2388 (47.7%) were ineligible for the trial and 2616 (52.3%) had not been enrolled to JCOG0707 despite being eligible (“Eligible” cohort). Of the 5004 patients, 1659 (33.2%) received adjuvant chemotherapy, mainly UFT (1550 of 1659, or 93.4% of those received any adjuvant chemotherapy).

      The 5-year survival rates (5yOS) for All and Eligible cohorts were 83.9% and 89.1%, respectively, versus 89.2% in the JCOG cohort. The 5yOS with UFT adjuvant were 89.4% in Eligible and 88.9% in JCOG cohorts, respectively.

      UFT administration was a significant prognostic factor in All (adjusted HR=0.66, p<0.0001), but not in Eligible cohort (adjusted HR=0.88, p=0.28). The patients were classified into 3 subgroups, those with tumors without GGA (ground-glass area, non-invasive component; GGA-), with GGA (GGA+) and tumor size < 3 cm, and GGA+ with tumor size > 3cm. 5yOS of 744 patients in the Eligible cohort with GGA+ and tumor size < 3cm were excellent, 96.9%/96.4% with/without UFT. For 416 patients with GGA+ tumor sized > 3cm in Eligible cohort, invasive tumor size in the pathological specimen was prognostic but not predictive for UFT effect. When the invasive tumor size was >3 cm, 5yOS with/without UFT were 90.0/87.8%, whereas when it was <3 cm, 5yOS with/without UFT were 96.2/96.2%. UFT tended to be associated with better prognosis in 1389 patients with GGA- tumor when the tumor size was >3 cm, (5yOS 83.8% vs 77.4%, adjusted HR=0.82, p=0.27), but not when it was <3 cm (5yOS 88.1% vs 88.1%, adjusted HR=0.97, p=0.87).

      Conclusion

      Our “real-world” data reproduced the survival outcome of JCOG0707, especially in Eligible cohort. Invasive tumor size was a prognostic factor in GGA+ tumors, suggesting validity of the 8th IASLC TNM classification. GGA+ tumor with invasive tumor size of <3 cm would not require any adjuvant therapy. UFT effect appears to be limited to large GGA- tumor.