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Konstantin Laktionov
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-107 - Comparison of Outcomes in Responders and Nonresponders to Nivolumab as 2+ Line Treatment in Advanced Refractory NSCLC Pts (ID 550)
08:00 - 18:00 | Presenting Author(s): Konstantin Laktionov
- Abstract
Background
The extent to which treatment response to immunotherapy translates into quality-adjusted survival time in NSCLC pts is worthwhile. We aimed to evaluate survival outcomes adjusted to quality of life (QoL) in NSCLC pts who are responders (Rs) and nonresponders (nRs) to nivolumab (Nivo) as 2+ line treatment within expanded access program and in a real-world practice.
Method
Adult pts with advanced platinum refractory NSCLC were enrolled in 11 centers in RF. All the pts received Nivo 3 mg/kg q2w. Tumor response was assessed using RECIST v. 1.1, adverse events (AEs) – NCI CTCAE v3.0. Pts with complete/partial response or disease stabilization (CR/PR or SD) at first tumor evaluation were considered as Rs, with progression or early death due to disease – as nRs. For QoL assessment pts filled out RAND SF-36 at different times during Nivo treatment. Overall survival (OS) and progressive-free survival (PFS) curves were evaluated by the Kaplan-Meyer method and compared by the log-rank test. Quality-adjusted outcomes in Rs and nRs were compared using Q-TWiST method. UTWiST and UREL were calculated on the basis of SF6D.
Result
Overall, 200 pts were included in the analysis: 65% – males; median age – 62 y.o.; ECOG 0-1 – 81%; former/current smokers – 70.5%; non squamous NSCLC – 64%; ≥2 lines of previous treatment – 53%. Median follow-up – 7.5 mos; 195 pts completed Nivo treatment at cut-off. Out of 200 pts response was not evaluated in 7 pts; among 193 pts 58% were categorized as Rs, 42% – nRs (the median evaluation time – 2.1 mos). Responder status was not significantly associated with demographics, smoking status, or baseline ECOG. Median duration of PR/SD in Rs – 4.4 mos (CI 95% 0.7-33.4). Median follow-up in nRs – 1.8 mos (CI 95% 0.26-4.21). As compared with nRs, Rs had longer median OS (18.7 vs 3.5 mos, p<0.001) and PFS (9.1 vs 1.8 mos, p<0.001) as well as longer TWiST (mean 12.5 vs 1.9 mos, 95%CI of difference 8.4–12.9). Mean Q-TWiST in Rs was 11.8 mos vs 4.8 mos in nRs with 7.0 mos gain. Relative Q-TWiST gain is 88%.
Conclusion
The results obtained in this observational study demonstrate acceptable treatment outcomes of Nivo in advanced refractory NSCLC pts. Response to Nivo treatment is significantly associated with better median PFS and OS and accompanied with better quality-adjusted survival outcomes in this difficult patient cohort. The Q-TWiST provides a comprehensive assessment of the benefit of response to immunotherapy into quality-adjusted survival in NCSLC pts.
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EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.14-51 - Lorlatinib in Crisotinib-Resistant ALK+ NSCLC Patients. Our Experience (ID 1630)
08:00 - 18:00 | Presenting Author(s): Konstantin Laktionov
- Abstract
Background
Background: Lorlatinib is the third generation inhibitor of ALK and ROS1 tyrosine kinase has shown activity in patients with crisotinib-refractory ALK-positive NSCLC most of whom had CNS metastases . We report results of the overall and intracranial antitumor activity of patients with crisotinib-refractory ALK-positive NSCLC.
Method
Patients with ALK and ROS1-positive NSCLC who had progressed after crisotinib and at least one regimen of chemotherapy with or without CNS metastases with ECOG PS was 0-2 and adequate organ functions were given lorlatinib 100 mg orally once daily continuously. Primary endpoint - overall and intracranial objective response, secondary endpoint – safety of lorlatinib.
Since January 2017 to July 2018 39 patients were enrolled: ALK+- 36, ROS1+ - 3 pts. Median age 49 years. Patient characteristics summarised in Table 1.
Table 1. Baseline characteristics
Result
Objective response was achieved in 22 pts (56, 4%) – 3 complete (7,7%) and 19 partial (48,7%) responses. 16 pts( 41%) had stabilization as the best response, 1 ALK+ pt progressed. So disease control is 97,4%. Among 27 pts with brain metastases intracranial objective responses were observed in 20 pts (74%), included 8 complete (30%) and 12 patial responses (44%), 7 pts (26%) had stable disease . Thus all pts with intracranial lesions had disease control . 18 pts underwent previous brain radiotherapy of whom 12 pts received whole-brain radiotherapy, 5pts - stereotactic radiosurgery, and 1 received both. Their objective intracranial response was 61%. All patients without previous brain radiotherapy had objective intracranial response (100%).
At data cut-off (20.03.2019) median duration of treatment was 12 mon. 6 pts stopped receiving lorlatinib: 4 due to disease progression and 2 due to the deterioration of concurrent diseases.
Side effects of lorlatinib were mild or moderate. The most frequent events were hypercholesterolaemia (82%, 3-4 grade 25%), oedema ( 71,8%), weight increased ( 38.5%). Only 5 pts (12.8%) needed in dose reduction.
Conclusion
Our results confirmed that lorlatinib is an effective treatment option for pretreated ALK+/ROS1+ patients with high intracranial activity and good safety profile.
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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): Konstantin Laktionov
- 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): Konstantin Laktionov
- 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.
