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Seiji Niho
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MA 17 - Locally Advanced NSCLC (ID 671)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:S. Jheon, Georgios Stamatis
- Coordinates: 10/17/2017, 15:45 - 17:30, F203 + F204 (Annex Hall)
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MA 17.06 - Safety Data from Randomized Phase II Study of CDDP+S-1 vs CDDP+PEM Combined with TRT for Locally Advanced Non-Squamous NSCLC (ID 8296)
15:45 - 17:30 | Author(s): Seiji Niho
- Abstract
- Presentation
Background:
Both cisplatin (CDDP)+S-1 and CDDP+pemetrexed (PEM) can be given at full systemic doses with thoracic radiotherapy (TRT) in locally advanced non-small cell lung cancer (NSCLC), and CDDP+PEM is one of the standard chemotherapy regimens in patients with advanced non-squamous (non-sq) NSCLC. This multicenter, randomized, open-label, phase II study (SPECTRA) compared the efficacy and safety of the two above-mentioned promising regimens combined with TRT in patients with unresectable locally advanced non-sq NSCLC.
Method:
Patients were randomly assigned to receive CDDP+S-1 (CDDP 60mg/m2, d1, and S-1 80mg/m2, d1-14, q4w, up to 4 cycles) or CDDP+PEM (CDDP 75mg/m2, d1, and PEM 500mg/m2, d1, q3w, up to 4 cycles) combined with TRT 60Gy in 30 fractions. The primary endpoint was 2-year progression-free survival (PFS) rate. If the 2-year PFS rate is assumed to be 25% in the inferior therapy group and 15% higher in the superior therapy group of this study, the sample size needed for selection of the optimum treatment group at a probability of approximately 95% will be 51 cases/group with the Simon’s selection design. The sample size was set at 100 patients.
Result:
Between Jan 2013 and Oct 2016, 102 patients were enrolled in this study from 9 institutions in Japan. All 102 patients were eligible and assessable, of whom 52 were assigned to CDDP+S-1 and 50 to CDDP+PEM. Baseline characteristics were similar (CDDP+S-1/CDDP+PEM): median age (range) 64.5 (39-73)/63.5 (32-74) years; women, n=17 (33%)/n=17 (34%); stage IIIB, n=21 (40%)/n=20 (40%); ECOG PS of 1, n=14 (27%)/n=14 (28%); never smoker, n=12 (23%)/n=12 (24%); and adenocarcinoma, n=47(90%)/n=45(90%). Completion rate of TRT (60Gy) and chemotherapy (4 cycles) was 92%/98% and 73%/86%, respectively. Response rate was 60%/64%. Grade 3 or higher toxicities included febrile neutropenia (12%/2%), anorexia (8%/16%), diarrhea (8%/0%), esophagitis (6%/8%), pneumonia (4%/4%), neutropenia (38%/52%), anemia (8%/12%), thrombocytopenia (4%/6%), and hyponatremia (12%/12%). Grade 1 radiation pneumonitis was observed in 8 (15%)/2 (4%) patients on the basis of the data collected 30 days or less after the discontinuation of protocol treatment. No treatment-related death was observed. The data on PFS and overall survival are immature.
Conclusion:
Response rate was similar between the two arms. Toxicities were tolerable and manageable in both arms; however febrile neutropenia was more frequently observed in the CDDP+S-1 arm. We will present the updated safety data of this study at the conference. Survival data will be analyzed in late 2018.
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MS 07 - Neuroendocrine Tumors other than SCLC: Pathology to Patient Management (ID 529)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:C. Barrios, Sang-We Kim
- Coordinates: 10/16/2017, 15:45 - 17:30, F203 + F204 (Annex Hall)
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MS 07.02 - Novel Chemotherapy for LCNEC (ID 7670)
15:45 - 17:30 | Presenting Author(s): Seiji Niho
- Abstract
- Presentation
Abstract:
Given that large cell neuroendocrine carcinoma (LCNEC) of the lung is rare and histological diagnosis from small samples is difficult, no large-scale clinical trials has yet evaluated the optimal chemotherapy for LCNEC. In a retrospective study of 45 consecutive patients with advanced LCNEC, response rates for small cell lung cancer (SCLC; n=11) and non-small cell lung cancer (NSCLC; n=34) regimen groups receiving first-line chemotherapy were 73% and 50% (P=0.19), median progression-free survival (PFS) was 6.1 and 4.9 months (P=0.41), and median overall survival (OS) was 16.5 and 9.2 months (P=0.19), respectively. SCLC regimens included platinum plus paclitaxel (PTX) and irinotecan plus platinum, while NSCLC regimens included pemetrexed, erlotinib, and gemcitabine[1]. A second retrospective study of the efficacy of first-line chemotherapies in 22 consecutive patients with advanced LCNEC reported an objective response in five of nine patients receiving CDDP+irinotecan (56%) and in three of five receiving carboplatin (CBDCA)+PTX (60%) [2]. Of the two prospective phase II studies of platinum-based chemotherapies for LCNEC (Table), a French study (GFPC 0302) used a chemotherapy regimen comprising CDDP+etoposide (ETP), while a Japanese study used CDDP+irinotecan. Objective response rate (ORR) was about 40% and median PFS was 5 to 6 months in both studies. Central pathological reviews in both studies demonstrated that about a quarter of patients had SCLC or undifferentiated NSCLC [3, 4]. Everolimus is an oral mTOR inhibitor that has been approved for the treatment of well-differentiated neuroendocrine tumors of the lung. A recent phase II study of CBDCA+PTX+everolimus as first-line chemotherapy for advanced LCNEC was discontinued prematurely due to low recruitment after enrolling only 49 patients versus a planned sample size of 71. Among them, ORR was 45%, disease control rate was 74%, median PFS was 4.4 months, and median OS was 9.9 months [5]. Ongoing studies include a randomized phase II study comparing CBDCA+ETP and CBDCA+PTX for advanced LCNEC and a randomized phase II/III study of CDDP+ETP with or without veliparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in patients with extensive stage SCLC or metastatic LCNEC.
Reference 1. Sun JM, Ahn MJ, Ahn JS, et al. Chemotherapy for pulmonary large cell neuroendocrine carcinoma: similar to that for small cell lung cancer or non-small cell lung cancer? Lung Cancer 2012;77:365-370. 2. Fujiwara Y, Sekine I, Tsuta K, et al. Effect of platinum combined with irinotecan or paclitaxel against large cell neuroendocrine carcinoma of the lung. Jpn J Clin Oncol 2007;37:482-486. 3. Niho S, Kenmotsu H, Sekine I, et al. Combination chemotherapy with irinotecan and cisplatin for large-cell neuroendocrine carcinoma of the lung: a multicenter phase II study. J Thorac Oncol 2013;8:980-984. 4. Le Treut J, Sault MC, Lena H, et al. Multicentre phase II study of cisplatin-etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study. Ann Oncol 2013;24:1548-1552. 5. Christopoulos P, Engel-Riedel W, Grohe C, et al. Everolimus with paclitaxel and carboplatin as first-line treatment for metastatic large-cell neuroendocrine lung carcinoma: a multicenter phase II trial. Ann Oncol 2017.Study GFPC 0302 Japanese study German study Regimen CDDP+ETP CDDP+Irinotecan CBDCA+PTX+Everolimus N 42 44 49 ORR (%) (95%CI) 38 55 (39-70) 45 (31-60) Median PFS (months) (95%CI) 5.2 (3.1-6.6) 5.9 (5.5-6.3) 4.4 (3.2-6.0) Median OS (months) (95%CI) 7.7 (6.0-9.6) 15.1 (11.2-19.0) 9.9 (6.9-11.7)
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OA 05 - Next Generation TKI (ID 657)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:James Chih-Hsin Yang, Fiona Blackhall
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 301 + 302
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OA 05.01 - First-Line Dacomitinib versus Gefitinib in Advanced Non-Small-Cell Lung Cancer with EGFR Mutation Subgroups (ID 8555)
15:45 - 17:30 | Author(s): Seiji Niho
- Abstract
- Presentation
Background:
The ARCHER 1050 study (NCT01774721) demonstrated benefits of dacomitinib compared with gefitinib as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) and EGFR-activating mutation. Here, we present the results of a prospective subgroup analysis by EGFR mutation subtype.
Method:
In this ongoing phase 3, open-label study, eligible patients with newly diagnosed stage IIIb/IV or recurrent NSCLC and EGFR-activating mutation (exon 19 deletion or L858R mutation ± T790M mutation) with an Eastern Cooperative Oncology Group performance status of 0–1 were randomized (1:1) to receive dacomitinib or gefitinib, stratified by race and EGFR mutation subtype. The primary endpoint was progression-free survival (PFS) by blinded independent radiologic central (IRC) review. Secondary endpoints included overall survival and objective response rate (ORR), as determined by IRC and investigators’ assessments.
Result:
A total of 452 patients were randomized (dacomitinib, n=227; gefitinib, n=225). Among the dacomitinib and gefitinib arms, respectively, 134 (59%) and 133 (59%) had exon 19 deletions and 93 (41%) and 92 (41%) had L858R mutations. The Table shows PFS, ORR, and duration of response by EGFR mutation per IRC. Results based on investigators’ assessments were consistent with those based on IRC review. Overall survival data are immature.Exon 19 Deletion L858R Mutation Dacomitinib (n=134) Gefitinib (n=133) Dacomitinib (n=93) Gefitinib(n=92) PFS per IRC Median, months (95% CI) 16.5 (11.3–18.4) 9.2 (9.1–11.0) 12.3 (9.2–16.0) 9.8 (7.6–11.1) Hazard ratio (95% CI) 1-sided P value 0.551 (0.408–0.745) <0.0001 0.626 (0.444–0.883) 0.0034 ORR per IRC CR, n (%) 7 (5.2) 3 (2.3) 5 (5.4) 1 (1.1) PR, n (%) 95 (70.9) 90 (67.7) 63 (67.7) 67 (72.8) ORR (CR + PR), n (%) (95% CI) 102 (76.1) (68.0–83.1) 93 (69.9) (61.4–77.6) 68 (73.1) (62.9–81.8) 68 (73.9) (63.7–82.5) 1-sided P value 0.1143 0.5395 DoR in responders per IRC Median, months (95% CI) 15.6 (13.1–19.6) 8.3 (7.9–10.1) 13.7 (9.2–17.4) 7.5 (6.5–10.2) Hazard ratio (95% CI) 1-sided P value 0.454 (0.319–0.645) <0.0001 0.403 (0.267–0.607) <0.0001 CI, confidence interval; CR, complete response; DoR, duration of response; PR, partial response.
Conclusion:
By IRC and investigators’ assessments, PFS with dacomitinib was superior to that with gefitinib in patients with either EGFR mutation. Despite a similar ORR among the treatment and EGFR mutation subgroups, duration of response was longer with dacomitinib for both mutations.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-012 - Symptom Impact of First-Line Dacomitinib versus Gefitinib in EGFR-Positive NSCLC: Results from a Randomized Phase 3 Study (ID 8569)
09:30 - 16:00 | Author(s): Seiji Niho
- Abstract
Background:
Patients with non-small-cell lung cancer (NSCLC) experience high disease burden due to many cancer-related symptoms (eg, cough, dyspnea, pain, and fatigue). Decreasing tumor burden may reduce/delay symptoms and favorably impact global health-related quality of life (HRQoL). Dacomitinib is an irreversible, small-molecule inhibitor of EGFR/HER-1, HER-2, and HER-4 tyrosine kinases. In a global, multicenter, randomized, open-label phase 3 study (NCT01774721) for first-line treatment of NSCLC, dacomitinib improved the primary objective of progression-free survival per independent radiologic review (median, 14.7 vs 9.2 months; hazard ratio, 0.59; 95% confidence interval [CI], 0.47–0.74; P<0.0001) over gefitinib. Median duration of treatment was longer with dacomitinib than with gefitinib (67 vs 52 weeks, respectively).[1] A secondary objective was to explore HRQoL. Here, we report the impact of dacomitinib and gefitinib treatment on core lung cancer symptoms.
Method:
Patients were randomized 1:1 to receive oral dacomitinib (45 mg) or gefitinib (250 mg) once daily. Disease-related symptoms were measured using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire–Core 30 (QLQ-C30) and Lung Cancer 13 (QLQ-LC13). Scores were summarized by the mean and 95% CI for each group and plotted over 30 cycles and at the end of treatment; the number of cycles (n=30) chosen for this analysis was not prespecified. Mean changes from baseline (cycle 1, day 1 [C1D1]) were reported for each group.
Result:
Between 9-May-2013 and 20-March-2015, 452 patients were randomly assigned to dacomitinib (n=227) or gefitinib (n=225). Baseline scores were similar between treatment arms. On-study completion rates were high, with >90% of patients answering all questions for most treatment cycles. Statistically significant improvements from baseline (95% CI excludes 0; no adjustment for multiplicity) for most cycles were seen in fatigue, pain, dyspnea, and cough in both arms. Improvements were reported as early as C1D8. Clinically meaningful improvements (≥10 points score change) were recorded for pain in chest (23/30 cycles) and cough (28/30 cycles) with dacomitinib and for cough (22/30 cycles) with gefitinib; hence, improvements appear to be more frequent with dacomitinib. Symptom burden at end of treatment was generally higher than during treatment. As treatment duration was longer with dacomitinib, key lung cancer symptom improvements were seen for a longer time in patients treated with dacomitinib.
Conclusion:
Dacomitinib, along with gefitinib, demonstrated favorable clinical benefit and improvements in key NSCLC symptoms. These findings are important when considering choice of therapy. Reference 1. Mok T, et al. J Clin Oncol. 2017;35(Suppl):abstract LBA9007.
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P3.01-072 - Dacomitinib Versus Gefitinib for First-Line Treatment of Advanced EGFR+ NSCLC in Japanese Patients (ARCHER 1050) (ID 8476)
09:30 - 16:00 | Author(s): Seiji Niho
- Abstract
Background:
Second-generation EGFR tyrosine-kinase inhibitor dacomitinib has shown encouraging activity as first-line therapy in patients with EGFR-activating mutation-positive (EGFR[+]) advanced NSCLC. We performed the first randomized, open-label phase 3 trial comparing dacomitinib with gefitinib as first-line therapy (NCT01774721) which demonstrated a clinically meaningful and statistically significant benefit of dacomitinib versus gefitinib (PFS per IRC: HR, 0.59 [95%CI, 0.47–0.74]; 1-sided P<0.0001; median PFS, 14.7 vs 9.2 months). We present results from Japanese patients enrolled in this ongoing study.
Method:
Patients with newly diagnosed stage IIIB/IV recurrent NSCLC harboring an EGFR-activating mutation (exon 19 deletion or exon 21 L858R ± exon 20 T790M) were randomized 1:1 to once-daily oral dacomitinib 45 mg or gefitinib 250 mg until disease progression or discontinuation. Patients with CNS mets excluded. Stratification was by race and EGFR mutation subtype. The primary endpoint was progression-free survival (PFS) per blinded independent review committee (IRC).
Result:
Among 452 patients enrolled in ARCHER 1050, 81 were Japanese. Slight imbalances in baseline characteristics were observed (Table). PFS and duration of response improvement in Japanese patients was consistent with global results.
Objective response rates per IRC were similar (dacomitinib, 75.0% [95%CI, 58.8–87.3]; gefitinib, 75.6% [95%CI, 59.7–87.6]; 2-sided P=0.9579). Overall survival data are not mature. All 81 patients received study treatment. No grade 4/5 adverse events (AEs were observed with dacomitinib, while 3 grade 4 AEs and 1 grade 5 AE (disease progression) occurred with gefitinib. The most common grade 3 AEs were dermatitis acneiform (27.5%) and paronychia (22.5%) with dacomitinib and alanine aminotransferase increased (12.2%) and abnormal hepatic function (7.3%) with gefitinib. No new safety signals were identified.Japanese Intention-to-Treat Population Dacomitinib (n = 40) n (%) Gefitinib (n = 41) n (%) Unstratified HR [95% CI] 1-sided p-value Male 15 (37.5) 20 (48.8) Age, years <65 ≥65 19 (47.5) 21 (52.5) 15 (36.6) 26 (63.4) Smoking status Never smoked Ex-smoker Smoker 19 (47.5) 20 (50.0) 1 (2.5) 24 (58.5) 16 (39.0) 1 (2.4) ECOG PS 0 1 28 (70.0) 12 (30.0) 21 (51.2) 20 (48.8) Median, months Median, months PFS per IRC 18.2 (95% CI, 11.0–31.3) 9.3 (95% CI, 7.4–14.7) 0.54 (95% CI, 0.31–0.95) P=0.0141 PFS per INV 18.3 (95% CI, 14.6–22.1) 10.2 (95% CI, 7.3–16.9) 0.61 (95% CI, 0.36–1.04) P=0.0334 DoR per IRC in responders # of responders=30 17.5 (95% CI, 10.2–34.3) # of responders=31 8.3 (95% CI, 5.6–12.9) 0.44 (95% CI, 0.22–0.84) P=0.0056 CI, confidence interval; DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; INV, investigator assessment.
Conclusion:
Dacomitinib significantly improved PFS and duration of response over gefitinib in first-line treatment of Japanese patients with advanced EGFR[+] NSCLC, with a manageable safety profile.
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P3.14 - Radiotherapy (ID 730)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.14-001 - Impact of PCI on Prognosis of LD-SCLC Through Pattern of Brain Metastases as a First Recurrence Site (ID 9648)
09:30 - 16:00 | Author(s): Seiji Niho
- Abstract
Background:
Brain metastases frequently occur in patients with small-cell lung cancer. Therefore, prophylactic cranial irradiation (PCI) is recommended for good responders of initial treatment. The purpose of this study was to investigate influence of PCI on pattern of brain metastases as a first recurrence site (BMFR) after radical treatment for limited disease small-cell lung cancer (LD-SCLC).
Method:
This retrospective study included LD-SCLC patients treated with thoracic radiotherapy and concurrent chemotherapy between January 2006 and December 2014. Induction chemotherapy was permitted. Thoracic radiotherapy was performed with accelerated hyper-fractionated radiotherapy (twice daily, 45 Gy in 30 fractions over 3 weeks) or conventional-fractionated radiotherapy (once daily, 50 Gy in 25 fractions over 5 weeks). Regimen of chemotherapy consisted of intravenous platinum-etoposide.
Result:
One hundred and sixty-two patients were included in this study. The median follow-up duration for surviving patients was 38 months (range, 6-105 months). Among 123 patients (76%) who died, 104 patients died due to disease progression, 11 died due to unknown cause and 8 died due to other cause. Ninety-three patients (57%) underwent PCI, and the 3-year disease specific survival (DSS) rates were 20%(12-35) in patients without PCI and 43%(33-55) in those with PCI (p<0.001). Concerning the recurrence pattern, the frequency of BMFR was significantly higher in patients who did not underwent PCI compared with those who did (49% vs 25%, p=0.008) although no significant difference in frequency of all site of recurrence was observed between patients without PCI and those with PCI (83% vs 73%, p=0.109). Regarding the impact of BMFR on prognosis, patients with BMFR exhibited significant shorter DSS than those whose first recurrence sites was other than brain metastases (3yr-DSS 6% vs 22%, p=0.007), and patients who developed BMFR without PCI exhibited significant lower DSS compared with those who developed BMFR with PCI (3yr-DSS 0% vs 17%, p=0.005). In addition, 68% of patients who did not underwent PCI exhibited multiple BMFR lesions with 5 or more while 12% of patients who did (p<0.001).
Conclusion:
The results of this study indicated that BMFR exhibited significant negative impact on prognosis after radical treatment for LD-SCLC and the difference in the number of metastatic lesions in BMFR between patients with PCI and those without PCI might affect clinical outcomes.
