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Artem Poltoratskiy
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-62 - Afatinib in EGFR TKI-Naïve Patients with EGFR Mutation-Positive NSCLC: Combined Analysis of Two Single-Arm Phase IIIb Studies (ID 1338)
09:45 - 18:00 | Author(s): Artem Poltoratskiy
- Abstract
Background
First-line afatinib significantly improved progression-free survival (PFS) compared with platinum-doublet chemotherapy in patients with EGFR mutation-positive (EGFRm+; including uncommon mutations) NSCLC in two Phase III studies (LUX-Lung 3: median 11.1 vs 6.9 months, hazard ratio [HR]=0.58; p=0.001; LUX-Lung 6: 11.0 vs 5.6 months, HR=0.28; p<0.0001). First-line afatinib also significantly improved PFS compared with gefitinib in the Phase IIb LUX-Lung 7 study (11.0 vs 10.9 months, HR=0.73; p=0.017). However, some patients still receive chemotherapy as a first-line treatment choice in clinical practice. Here, we report a combined analysis of outcomes from two large Phase IIIb studies of afatinib in EGFR TKI-naïve patients treated in a setting similar to real-world practice.
Method
In both studies, EGFR TKI-naïve, including chemotherapy-pretreated, patients with locally advanced or metastatic EGFRm+ NSCLC received 40 mg/day afatinib until progressive disease or lack of tolerability (dose reduction was permitted [minimum: 20 mg/day]). Study 1 enrolled patients across eight European countries, and Russia, Israel and Australia; Study 2 enrolled patients from centres in China, Hong Kong, India, Singapore, and Taiwan. Interim (Study 1; data cut-off: 30 April 2018) and final (Study 2; data cut-off: 06 July 2018) data were used for this combined analysis of time to symptomatic progression (TTSP), PFS, objective response, and safety.
Result
A total of 1020 patients were treated with afatinib (female: 59%; Asian/White/other: 54%/46%/<1%; median age [range]: 61 years [25–89]; ECOG PS 0/1/2: 26%/69%/5%; common/uncommon EGFR mutations: 82%/18%; treatment line 1st/2nd/≥3rd: 69%/23%/8%; presence of brain metastases: 18%). Overall, median TTSP was 14.6 months (95% confidence interval [CI]: 13.8–15.8 months); median PFS was 12.9 months (95% CI: 11.6–13.7 months). Objective response rate was 52.7%. Adverse events (AEs; all grade/grade ≥3) occurred in 1012/556 (99%/55%) patients; serious AEs were reported in 366 patients (36%). The most common grade ≥3 AEs were diarrhoea (14%) and rash (9%). Any-cause AEs leading to dose reduction were reported in 412 (40%) patients. Treatment discontinuation due to afatinib-related AEs occurred in 54 patients (5%).
Conclusion
In this combined analysis of two large, prospective ‘real-world’ afatinib studies in EGFR TKI-naïve patient populations, which included patients treated with afatinib in later lines, patients with ECOG PS 2, patients with brain metastases, and patients with uncommon mutations, safety data were consistent with previous results seen in the LUX-Lung 3, 6, and 7 studies. Efficacy findings are also encouraging, with a median TTSP of 14.6 months.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-58 - A Phase IIIb, Open-Label Study of Afatinib in Caucasian EGFR TKI-Naïve Patients with EGFRm+ NSCLC: An Interim Analysis (ID 1371)
10:15 - 18:15 | Author(s): Artem Poltoratskiy
- Abstract
Background
First-line afatinib demonstrated significantly improved median PFS in patients with EGFR mutation-positive (EGFRm+) NSCLC versus chemotherapy in LUX-Lung 3/6 (HR [95% CI]: 0.58 [0.43–0.78]/0.28 [0.20–0.39]), and versus gefitinib in LUX-Lung 7 (0.73 [0.57–0.95]). Since these trials had strict inclusion criteria, it is important to support these findings with real-world studies of broader patient populations. We report interim results of a Phase IIIb study of afatinib treatment for EGFRm+ NSCLC in a patient population similar to real-world practice.
Method
EGFR TKI-naïve patients with locally advanced/metastatic EGFRm+ NSCLC, and ECOG PS 0–2, received afatinib 40 mg/day. Dose reduction was permitted (minimum 20 mg/day). Primary endpoint: adverse events (AEs; descriptive fashion). Efficacy was also assessed.
Result
At data cut-off (30-April-2018), 479 patients were enrolled and treated (Caucasian/Asian/other: 97%/2%/<1%; ECOG PS 0–1/2: 92%/8%; 1st/2nd/≥3rd-line therapy: 78%/17%/5%; common/uncommon mutations: 87%/13%; brain metastases: 17%). Median time on afatinib: 359 days. Objective response and disease control rates were 46% and 86%, respectively. Other efficacy outcomes are in the Table. The most common grade ≥3 afatinib-related AEs were diarrhoea (16%) and rash (11%). 258 (54%) patients had AEs leading to dose reduction (most frequently diarrhoea [25%]/rash [11%]), and 37 (8%) had TRAEs leading to discontinuation (most frequently diarrhoea [3%]; all others [<1%]). Serious afatinib-related AEs occurred in 39 (8%) patients.
Median TTSP, months
(95% CI)
Median PFS, months
(95% CI)
All pts (n=479)
14.9
(13.8–17.6)
13.4
(11.8–14.5)
Line of therapy
1st (n=374)
15.6
(14.1–18.5)
13.8
(12.6–15.2)
2nd (n=81)
14.7
(11.3–20.6)
13.2
(8.3–17.7)
≥3rd (n=24)
8.1
(3.7–14.4)
6.6
(3.2–12.6)
Baseline brain metastases*
No (n=395)
15.8
(14.1–18.8)
13.9
(12.7–15.5)
Yes (n=83)
13.7
(9.7–17.2)
10.1
(8.2–13.9)
Baseline mutation type*
Common† (n=416)
15.9
(14.5–19.1)
14.1
(13.0–15.7)
Uncommon‡ (n=62)
6.7
(5.4–8.3)
5.9
(4.0–7.4)
Baseline ECOG PS*, including age
0–1 (n=442)
15.8
(14.4–18.8)13.8
(12.8–15.2)<65 years (n=221)
14.7
(12.7–17.6)13.4
(11.6–15.5)≥65 years (n=221)
18.9
(14.7–21.7)14.1
(12.6–16.4)2 (n=36)
8.9
(5.7–13.2)6.2
(2.5–11.6)<65 years (n=16)
6.0
(2.4–13.2)3.2
(1.5–9.1)≥65 years (n=20)
9.9
(7.6–13.9)7.7
(5.7–13.9)*Missing (n=1); †Del 19 and/or L858R with or without uncommon mutation; ‡Includes, n (%, of those with uncommon mutations): ex 20 ins: 37 (60), T790M: 12 (19), G719S/A/C: 12 (19), L861Q: 10 (16), S768I: 9 (15). TTSP, time to symptomatic progression; PFS, progression-free survival
Conclusion
This interim analysis indicated predictable and manageable safety, and encouraging efficacy, with afatinib in a broad patient population. The high proportion of patients with tumours harbouring exon 20 insertions may account for the differences in TTSP/PFS by common/uncommon mutation subgroup. Independent of treatment line, median TTSP/PFS in patients with ECOG PS 0–1 (LUX-Lung trials’ inclusion criteria) was 15.8/13.8 months, and, notably, was 18.9/14.1 months in those also aged ≥65 years. These findings by ECOG PS/age are consistent with those of the LUX-Lung trials.
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PL02 - Presidential Symposium including Top 7 Rated Abstracts (ID 89)
- Event: WCLC 2019
- Type: Plenary Session
- Track:
- Presentations: 1
- Now Available
- Moderators:Giorgio Vittorio Scagliotti, Ramon Rami-Porta
- Coordinates: 9/09/2019, 08:00 - 10:15, Barcelona (2005)
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PL02.11 - Overall Survival with Durvalumab Plus Etoposide-Platinum in First-Line Extensive-Stage SCLC: Results from the CASPIAN Study (Now Available) (ID 2265)
08:00 - 10:15 | Author(s): Artem Poltoratskiy
- Abstract
- Presentation
Background
Extensive-stage (ES)-SCLC is a recalcitrant disease associated with a median OS of ~10 months following etoposide-platinum (EP); new treatments that prolong survival are needed. CASPIAN (NCT03043872) is an open-label, phase 3 study of durvalumab (anti-PD-L1), ± tremelimumab (anti-CTLA-4), combined with EP as first-line treatment for patients with ES-SCLC. Here we report results for durvalumab + EP (D+EP) versus EP from a planned interim analysis.
Method
Patients with previously untreated ES-SCLC (ECOG PS 0/1) were randomised (1:1:1) to durvalumab 1500 mg + EP q3w; durvalumab 1500 mg + tremelimumab 75 mg + EP q3w; or EP q3w. Patients in immunotherapy arms received up to 4 cycles of EP followed by maintenance durvalumab until progression. Patients in the EP arm received up to 6 cycles of EP and prophylactic cranial irradiation (PCI), at the investigator’s discretion. Investigator’s choice of cisplatin or carboplatin was allowed across all arms and was a stratification factor at randomisation. The primary endpoint was OS. Data cutoff: 11 March 2019.
Result
268 patients were randomised to D+EP and 269 to EP. Baseline characteristics were well balanced between arms. In the EP arm, 56.8% of patients received 6 cycles of EP. At the interim analysis, D+EP significantly improved OS compared to EP with a HR of 0.73 (95% CI, 0.591-0.909; p=0.0047); mOS 13.0 versus 10.3 months, respectively. 33.9% of patients were alive at 18 months with D+EP versus 24.7% with EP. Secondary endpoints of PFS and ORR were also improved with D+EP compared to EP: PFS HR 0.78 (95% CI, 0.645-0.936); mPFS 5.1 versus 5.4 months; 12-month PFS rate 17.5% versus 4.7%; investigator-assessed ORR (RECIST v1.1; unconfirmed) 79.5% versus 70.3% (odds ratio, 1.64 [95% CI, 1.106-2.443]). The incidences of grade 3/4 AEs (61.5% versus 62.4%) and AEs leading to discontinuation (9.4% each) were similar between arms; the incidence of haematological toxicities was numerically higher in the EP arm. The durvalumab + tremelimumab + EP arm continues blinded to final analysis.
Conclusion
The addition of durvalumab to EP as first-line treatment for ES-SCLC significantly improved OS (27% reduction in risk of death) versus a robust control arm that permitted up to 6 cycles of EP and PCI. Of note, this chemo-immunotherapy regimen offers flexibility in platinum choice (carboplatin or cisplatin), reflecting current clinical practice for this challenging disease. No new safety signals were identified.
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