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Gee-Chen Chang
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-11 - Named Patient Use Program for Afatinib in Advanced NSCLC with Progression on Prior Therapy: Experience from Asian Centers (ID 12968)
16:45 - 18:00 | Author(s): Gee-Chen Chang
- Abstract
Background
A global named patient use (NPU) program for afatinib in patients with advanced/metastatic NSCLC who had progressed during prior therapy was conducted between May 2010 and January 2016 (Cappuzzo F et al, Future Oncol 2018). Here we describe treatment outcomes for patients at Asian centers.
a9ded1e5ce5d75814730bb4caaf49419 Method
Eligible patients had progressed after clinical benefit on prior erlotinib/gefitinib and/or had an activating EGFR/HER2 mutation, had exhausted all other treatments, and were ineligible for afatinib trials. Patients received afatinib (starting dose:30-50 mg/day). Dose modifications were allowed as tolerated. Time to treatment failure (TTF) was calculated from treatment initiation to discontinuation. Adverse event (AE) reporting was mandatory.
4c3880bb027f159e801041b1021e88e8 Result
Data were collected from 2242 NSCLC patients across 10 Asian countries. Patients were heavily pretreated, 62% received ≥2 prior chemotherapy lines, and for most, afatinib was 4th-line therapy; almost all had received erlotinib/gefitinib (Table 1). 97% of patients with known tumor status were EGFR mutation-positive (m+). Median TTF was 7.6 months overall, and 7.2 months in patients with EGFR m+ tumors (Table 1). TTF was >12 months in patients with EGFR exon20 insertions and Her2 mutations. ORR was numerically higher in patients with exon20 insertions and G719X/L861Q/S761I mutations than other subgroups (Table 1). Disease control rate was 78% overall. The most frequently reported AEs were rash and diarrhea; no new/unexpected safety signals were identified.
Table 1. Named patient use (NPU) program for afatinib in advanced/metastatic NSCLC: results from Asian centers Total number of patients 2242 Age; years, median 61 Female/male; % 60/40 Any prior treatment; n (%) 2223/2242 (99.2) Prior erlotinib and/or gefitinib; n (%) 2202/2223 (99.1) Prior erlotinib only; n (%) 866/2202 (39) Prior gefitinib only; n (%) 927/2202 (42) Prior lines of chemotherapy ≥3, 32%; ≥2, 62%; 1, 23%; 0, 15% Prior lines of systemic therapy ≥4, 37%; ≥3, 65%; 2, 21%; 1, 14%; 0, 0% EGFR m+; n (%) 1240/1281 (97) Specified EGFR mutation; n (%) 1101/1240 (89) TTF; months* n ORR, % n All patients with data available 7.6 1550 24.4 431 EGFR m+ 7.2 834 27.7 267 EGFR mutation specified 6.5 740 - - Common mutations (Del19 or L858R) 6.4 692 27.4 230 Uncommon mutations (all) 8.0 84 30.3 33 T790M 6.0 34 21.1 19 G719X, L861Q, or S761I 7.8 28 42.9 7 Exon 20 insertion 18.0 25 42.9 7 Her2 m+ 12.2 12 14.2 7 p.A775 G776insYVMA 12.4 7 25.0 4 *median
m+ve, mutation-positive; ORR, objective response rate;
TTF, time to treatment failure
8eea62084ca7e541d918e823422bd82e Conclusion
This analysis from Asian countries in the afatinib NPU program revealed clinically meaningful TTF/ORR in this heavily pre-treated and refractory advanced NSCLC patient population, including activity in common and uncommon EGFR mutations. TTF was numerically longer in patients with uncommon mutations (particularly EGFR exon20 insertions) and HER2 mutations than in those with common EGFR mutations. The safety profile of afatinib was consistent with non-Asian centers.
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P1.01-62 - The Third Generation Irreversible EGFR Inhibitor HS-10296 in Advanced Non-Small Cell Lung Cancer Patients (ID 13138)
16:45 - 18:00 | Author(s): Gee-Chen Chang
- Abstract
Background
The epidermal growth factor receptor (EGFR) T790M mutation is the most common mechanism of drug resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with sensitizing EGFR mutations. The third generation irreversible EGFR inhibitor HS-10296 has been shown to be safe and effective against both EGFR TKI-sensitizing and T790M resistance mutations in preclinical studies.
a9ded1e5ce5d75814730bb4caaf49419 Method
A Phase I, open-label, multi-center clinical trial was conducted in patients with locally advanced or distant metastatic NSCLC who have progressed following prior therapy with EGFR TKIs. The study was consisted of dose-escalation cohorts (55, 110, 220 and 260 mg) and dose-expansion cohorts (55, 110 and 220 mg) with once daily oral administration of HS-10296. In each expansion cohort, tumor biopsies were collected for central determination of EGFR T790M status. Patients were assessed for safety, tolerability, pharmacokinetics and efficacy of HS-10296.
4c3880bb027f159e801041b1021e88e8 Result
A total of 117 patients (median age 60) received at least one dose of HS-10296 across multiple sites in China (43 patients), Taiwan (69 patients) and the United States (5 patients). Maximum tolerated dose（MTD）has not been reached in this study. The most common adverse events were grade1/2 rash, pyrexia, upper respiratory tract infection, constipation, diarrhoea and blood creatine phosphokinase elevation. Drug-related serious adverse events were anemia (0.8%), blood creatinine elevation (0.8%), anemiarhabdomyolysis (0.8%) and blood creatine phosphokinase elevation (0.8%) occurred mainly in the cohorts with higher doses at 220 mg or 260 mg, respectively. These data demonstrated favorable tolerability and safety of HS-10296 in patients enrolled. The pharmacokinetics of HS-10296 was dose proportional and the plasma half-life was 30.7~37.5 hours. Among 82 evaluable patients (18 in escalation cohorts and 64 in expansion cohorts) with the EGFR T790M mutation, the overall objective response rate (ORR) was 52.4% (43/82; 95% CI, 41.6 to 63.3), while disease control rate (DCR) was 91.5% (75/82; 95% CI, 85.4 to 97.5). 110mg cohort showed better DCR (97.2% VS. 86.1%) than 55mg cohort. Phase II study is ongoing with the dose at 110 mg.
8eea62084ca7e541d918e823422bd82e Conclusion
HS-10296 has the potential to provide clinical benefit to locally advanced or distant metastatic NSCLC patients with EGFR T790M mutation who had disease progression following prior therapy with EGFR TKIs.
(The study was sponsored by Jiangsu Hansoh Pharmaceutical Co., Ltd.; ClinicalTrials.gov number, NCT02981108)
6f8b794f3246b0c1e1780bb4d4d5dc53
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PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)
- Event: WCLC 2018
- Type: Plenary Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
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PL02.03 - Brigatinib vs Crizotinib in Patients With ALK Inhibitor-Naive Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L) (ID 11155)
08:30 - 08:40 | Author(s): Gee-Chen Chang
- Abstract
- Presentation
Background
Brigatinib has robust efficacy in crizotinib-resistant ALK+ NSCLC, exhibiting median progression-free survival (mPFS) of 16.7 months. We report results of the first interim analysis from the ALTA-1L study of brigatinib vs crizotinib in ALK TKI-naive, ALK+ NSCLC (NCT02737501).
This open-label, multicenter study enrolled patients with stage IIIB/IV ALK+ NSCLC based on local ALK testing (FDA approved/other). Eligible patients had ECOG PS 0–2, ≤1 prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor. Asymptomatic CNS metastases were allowed. All patients had systematic CNS imaging. Patients were randomized 1:1 to brigatinib 180 mg QD with 7-day lead-in at 90 mg or crizotinib 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)-assessed PFS (RECIST v1.1). Secondary efficacy endpoints included BIRC-assessed objective response rate (ORR), intracranial ORR (iORR), and intracranial PFS (iPFS). Interim analyses were planned at 50% and 75% of planned PFS events (n=198).
275 patients were randomized (brigatinib/crizotinib, n=137/138); median age (years) 58/60. 26%/27% received prior chemotherapy for advanced disease, and 29%/30% had baseline brain metastases. At data cut-off (19 February 2018), median follow-up brigatinib/crizotinib: 11.0/9.25 months; with 99 PFS events, brigatinib met the prespecified threshold for statistical superiority vs crizotinib in the primary endpoint, BIRC-assessed PFS (HR 0.49, 95% CI 0.33–0.74, log-rank P=0.0007); brigatinib mPFS was not reached (95% CI NR–NR) vs crizotinib 9.8 months (95% CI 9.0–12.9). Investigator-assessed PFS HR 0.45 (95% CI 0.30–0.68), log-rank P=0.0001. Table shows additional efficacy data. Most common treatment-emergent AEs grade ≥3: brigatinib: increased CPK (16.2%), increased lipase (13.2%), hypertension (9.6%); crizotinib: increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/pneumonitis: brigatinib, 3.7%; crizotinib, 2.2%. Discontinuations due to AE (brigatinib/crizotinib): 11.8%/8.8%.
Brigatinib showed a statistically and clinically significant improvement in PFS compared with crizotinib in ALK inhibitor–naive ALK+ NSCLC.
BIRC-Assessed Endpoint, % Brigatinib
(n=137)
Crizotinib
(n=138)
P-Value All patients ORRa 76 (68–83b) 73 (65–80b) Confirmed ORR 71 (62–78b) 60 (51–68b) 0.0678 With any intracranial CNS metastases (n=43) (n=47) iORRa 79 (64–90b) 23 (12–38b) Confirmed iORR 67 (51–81b) 17 (8–31b) <0.0001 Median iPFS, months NR (11–NRb) 6 (4–9b) 1-year iPFS 67 (47–80b) 21 (6–42b) HR 0.27 (0.13–0.54) <0.0001c With measurable intracranial CNS metastases (n=18) (n=21) iORRa 83 (59–96b) 33 (15–57b) Confirmed iORR 78 (52–94b) 29 (11–52b) 0.0028 aResponse, ≥1 assessment; b95% CI; cLog-rank.
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