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Nobuyuki Yamamoto
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MA03 - Clinomics and Genomics (ID 119)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Heather A Wakelee, Wilfried Ernst Erich Eberhardt
- Coordinates: 9/08/2019, 10:30 - 12:00, Colorado Springs (1994)
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MA03.11 - Chemotherapy After PD-1 Inhibitors Versus Chemotherapy Alone in Patients with Non–Small Cell Lung Cancer (WJOG10217L) (Now Available) (ID 409)
10:30 - 12:00 | Author(s): Nobuyuki Yamamoto
- Abstract
- Presentation
Background
Studies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response in patients with non–small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of subsequent chemotherapy after PD-1 inhibitors (CAP) compared with chemotherapy alone.
Method
We conducted a multicenter retrospective cohort study for patients with advanced or recurrent NSCLC who were treated at 47 institutions across Japan between 1 April 2014 and 31 July 2017 with chemotherapy (docetaxel with or without ramucirumab; S-1; or pemetrexed) either after PD-1 inhibitor therapy (CAP cohort) or alone (control cohort). The primary end point was objective response rate (ORR). Inverse probability weighting (IPW) was applied to adjust for potential confounding factors, including age, sex, smoking status, performance status, histology, EGFR or ALK genetic alterations, brain metastasis, and recurrence after curative radiotherapy.
Result
A total of 1439 patients (243 and 1196 in the CAP and control cohorts, respectively) was available for unadjusted analysis. Several baseline characteristics—including age, histology, EGFR or ALK alterations, and brain metastasis—differed significantly between the two cohorts. After adjustment for patient characteristics with the IPW method, ORR was 18.9% for the CAP cohort and 10.8% for the control cohort (ORR ratio, 1.75; 95% confidence interval [CI], 1.25–2.45; P = .001). Median PFS was 3.5 and 2.6 months for the CAP and control cohorts, respectively (hazard ratio [HR], 0.862; 95% CI, 0.743–0.998; P = .048). The PFS rate at 3, 6, and 12 months was 53.3%, 28.5%, and 4.6%, respectively, for the CAP cohort, and 44.3%, 19.7%, and 6.1% for the control cohort. Median OS was 9.8 months for the CAP cohort and 10.3 months for the control cohort (HR, 0.979; 95% CI, 0.813–1.179; P = .822).
Conclusion
After adjustment for selection bias using propensity score–weighted analysis, CAP showed a significantly higher ORR and longer PFS compared with chemotherapy alone, with the primary end point of ORR being achieved. However, these results did not translate into an OS advantage, and no PFS benefit was apparent at 12 months despite the improvement observed at 3 and 6 months. Our findings suggest that prior administration of PD-1 inhibitors may result in a synergistic antitumor effect with subsequent chemotherapy, but that such an effect is transient. CAP therefore does not appear to achieve durable tumor control or confer a lasting survival benefit.
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MA13 - Going Back to the Roots! (ID 139)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Maurice Perol, Kaoru Kubota
- Coordinates: 9/09/2019, 14:00 - 15:30, Vancouver (2003)
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MA13.06 - Ph3 Study of Maintenance Therapy with S-1 vs BSC After Induction Therapy with Carboplatin + S-1 for Advanced Squamous Cell Lung Cancer (WJOG7512L) (Now Available) (ID 563)
14:00 - 15:30 | Author(s): Nobuyuki Yamamoto
- Abstract
- Presentation
Background
Our previous phase 3 study established carboplatin plus the oral fluorinated pyrimidine formulation S-1 as a standard option for first-line treatment of advanced non–small cell lung cancer (NSCLC) (J Clin Oncol 2010; 28:5240). The importance of maintenance therapy for patients with advanced squamous NSCLC has been unknown, however.
Method
WJOG7512L was designed as a randomized phase 3 study to evaluate whether maintenance therapy with S-1 improves clinical outcome after induction therapy with carboplatin plus S-1 in such patients. Before randomization, patients received carboplatin (AUC of 5 on day 1 every 3 weeks) plus S-1 (40 mg/m2 twice per day on days 1 to 14 every 3 weeks) as induction therapy. Those who did not progress after four cycles of induction therapy were randomized to receive either S-1 plus best supportive care (BSC) or BSC alone. The primary objective was to confirm the superiority of S-1 plus BSC with regard to progression-free survival.
Result
Of the 365 patients enrolled, 347 participated in the induction phase and 131 of these individuals were randomized to receive S-1 plus BSC (n = 67) or BSC alone (n = 64). Baseline demographics and clinical characteristics of the subjects, including the response to induction therapy, were well balanced. Patients receiving S-1 plus BSC showed a significantly reduced risk of disease progression compared with those receiving BSC alone (hazard ratio [HR], 0.548; 95% confidence interval [CI], 0.374–0.802; P = 0.0019). Median overall survival from randomization did not differ significantly between the two arms: 17.8 months for BSC alone and 16.7 months for S-1 plus BSC (HR, 0.890; 95% CI, 0.583–1.357). Time to deterioration in quality of life also showed no significant difference (P = 0.8754 for FACT-TOI, P = 0.9016 for FACT-LCS). The incidence of adverse events during maintenance therapy was low, with neutropenia, anemia, and thrombocytopenia of grade 3 or 4 each occurring in ~1% to 4% of patients.
Conclusion
Maintenance with S-1 plus BSC is an effective and well-tolerated treatment option for patients with advanced squamous NSCLC.
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OA02 - A New Vision of Targets and Strategies (ID 120)
- Event: WCLC 2019
- Type: Oral Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:Frank Griesinger, Luis Paz-Ares
- Coordinates: 9/08/2019, 10:30 - 12:00, Seoul (2007)
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OA02.06 - The Sequential Therapy of Crizotinib Followed by Alectinib: Real World Data of 840 Patients with NSCLC Harboring ALK-Rearrangement (WJOG9516L) (Now Available) (ID 2145)
10:30 - 12:00 | Author(s): Nobuyuki Yamamoto
- Abstract
- Presentation
Background
Previous clinical trials demonstrated that alectinib (ALEC) had a longer time-to-progression than crizotinib (CRZ) in 1st-line settings. Information on long-term overall survival (OS), however, is still limited with a few studies having reported that the sequential strategy of “CRZ followed by other ALK-inhibitor” can provide extended OS. In Japan, ALEC was approved for a 1st-line setting earlier than in other countries.
Method
We reviewed the clinical data of ALK-rearranged NSCLC patients who received CRZ or ALEC between May 2012 and Dec 2016. Patients were divided into two groups according to the first-administered ALK inhibitor, the CRZ or ALEC group. In order to evaluate the efficacy of the sequential strategy of “CRZ followed by ALEC”, the combined time to treatment failure (TTF) was calculated in the CRZ group as defined by the sum of the “TTF of CRZ” plus the “TTF of ALEC” if patients were treated with ALEC followed by CRZ. In the ALEC group, the “TTF of ALEC” was calculated. The primary endpoint is the comparison between the combined TTF in the CRZ group with the TTF in the ALEC group.
Result
Of 864 patients enrolled from 61 institutions, 840 patients were analyzed. Median age was 61 (range, 20-94); 56% were female; and 95% had adenocarcinoma. There were 535/305 patients in the CRZ/ALEC group. In the CRZ group, 282 patients received ALEC after CRZ failure. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group; median, 34.4 vs 27.2 months (mo); hazard ratio (HR), 0.709 [95%CI;0.559- 0.899]; P=0.0044. However, there was no significant difference in OS between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group; median, 88.4 months vs. not reached; HR 1.048 [95%CI;0.758-1.451]; P=0.7770. In the whole population, the CRZ group had a significantly shorter OS than the ALEC group; median, 53.6 mo vs not reached HR, 1.821 [95%CI;1.372-2.415]; P<0.0001.
Conclusion
The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group, however, OS benefit of sequential therapy of CRZ followed by ALEC was not shown.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-04 - A Phase II Trial of Weekly Nab-Paclitaxel in the Salvage Setting for Advanced Non-Small Cell Lung Cancer: Results of NICE Salvage Study (ID 1534)
09:45 - 18:00 | Author(s): Nobuyuki Yamamoto
- Abstract
Background
The optimal treatment in patients with advanced non-small cell lung cancer (NSCLC) after failing second- or third-line chemotherapy, i.e. NSCLC in salvage setting, has yet to be established. A small study reported that solvent-based paclitaxel (sb-P) monotherapy was safe and efficacious and could be a treatment option for NSCLC in salvage setting (Anticancer Res 2005). Nanoparticle albumin-bound paclitaxel (nab-P) showed a higher overall response rate (ORR) and better tolerability than sb-P when combined with carboplatin (CBDCA) as a first-line chemotherapy (J Clin Oncol 2012). These results suggest that nab-P monotherapy could be better therapeutic option than sb-P monotherapy for NSCLC in salvage setting. We therefore planned NICE Salvage study aiming to assess the efficacy and safety of nab-P monotherapy for NSCLC patients in salvage setting.
Method
NICE Salvage study was a multicenter single arm phase II study. Eligibility criteria included patients aged >= 20 years, with PS 0-2 and adequate organ function, and who have failed two or three prior lines of chemotherapy including at least a platinum-containing regimen for pathologically-proven advanced NSCLC. Patients who had treatment history with sb-P or nab-P, or had tumors harboring EGFR mutation or ALK fusion gene were excluded. Nab-P was administered at a dose of 80 mg/m2 on days 1,8 and 15 of a 28-days cycle and repeated until progressive disease, unacceptable toxicity, or patient’s refusal. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), ORR, disease control rate (DCR), efficacy according to prior use of docetaxel, quality of life, and safety. The study is powered to detect a 1.5-month improvement in median PFS in the investigational arm beyond the 2.0-month median PFS estimated from historical data. Assuming a one-sided 0.10 level of Type I error and 80% power, target sample size is calculated at 35. (UMIN000016173).
Result
Thirty-eight patients were enrolled and a patient was excluded from efficacy and safety analysis. Patient’s characteristics (n = 38) were as follows: median age = 68 years, male/female = 31/7, adenocarcinoma/squamous cell carcinoma /others = 20/15/3. Median PFS and OS was 3.5 month (95% confidence interval (CI), 1.7-3.8), and 13.4 month (95%CI, 9.1-25.1), respectively. ORR and DCR were 10.8% (95%CI, 2.9-24.8 ) and 56.8% (95%CI, 38.3-71.3 ), respectively. Grade 3 or 4 treatment-related adverse events were neutropenia (10.8%), anemia (2.7%), hepatotoxicity (2.7%) and diarrhea (2.7%). One treatment-related death (pulmonary infection) was observed.
Conclusion
This study failed to meet predefined primary endpoint. However the results showed that nab-P monotherapy was moderately efficacious and well-tolerated, suggesting the need for further investigation for NSCLC in salvage setting.
