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Robin Cornelissen
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-42 - Osimertinib Treatment for Patients with EGFR exon 20 Insertion Positive Non-Small-Cell Lung Cancer (ID 14152)
16:45 - 18:00 | Author(s): Robin Cornelissen
- Abstract
Background
Epidermal growth factor receptor (EGFR) exon 20 insertions are identified in 4-10% of al EGFR mutations in non-small cell lung cancer (NSCLC) and are generally associated with primary resistance to first and second generation EGFR tyrosine kinase inhibitors (TKIs). In vitro and preclinical animal studies have shown that osimertinib exerts antitumor activity in EGFR exon 20 insertion positive NSCLC cell lines. We report on a cohort of advanced stage NSCLC patients, harboring an EGFR exon 20 insertion, that was treated with osimertinib.
a9ded1e5ce5d75814730bb4caaf49419 Method
17 patients with advanced NSCLC harboring an EGFR exon 20 insertion were treated with osimertinib 80 mg once daily, in four institutions in the Netherlands. Data were obtained retrospectively. EGFR mutation status was assessed by next-generation sequencing. Progression free survival (PFS), disease control rate (DCR) and objective response rate (ORR) were assessed using RECIST v1.1.
4c3880bb027f159e801041b1021e88e8 Result
Median age was 63 years (range 35 – 81), 71% was female and median number of prior systemic treatments was 1 (range 0 – 3). Ten patients (59%) received prior platinum-based chemotherapy, and 2 patients afatinib, one patient experienced stable disease for 11 months, the other patient showed progression. Among all patients treated with osimertinib, we observed 1 partial response, 13 patients with stable diseases and 3 with progressive disease as best response (ORR 6%). Two patients were still on osimertinib treatment at the cut-off date. Median PFS was 3.7 months (95% CI: 2.3 – 5.4 months). Six of seventeen patients (35%) achieved DCR at five months.
Patient
Number of prior treatments
Prior platinum based chemotherapy
Prior EGFR TKI
Best RECIST response
PFS (months)
1
2
Yes
no
SD
4.0
2
1
Yes
no
SD
1.6
3
2
Yes
no
PR
0.7
4
1
Yes
no
PR
0.7
5
2
Yes
no
SD
3.8
6
1
Yes
no
SD
3.0
7
3
Yes
no
SD
9.3
8
1
Yes
no
SD
17.0
9
1
No
no
SD
3.7
10
1
Yes
no
SD
17.2
11
0
No
no
PR
3.1
12
0
No
no
SD
2.6
13
0
No
no
SD
6.5
14
3
Yes
afatinib (SD)
SD
7.9
15
1
No
afatinib (PD)
PD
1.7
16
0
no
no
SD
8.3
17
0
no
no
SD
1.4
EGFR, epidermal growth factor receptor; RECIST: Response Evaluation Criteria in Solid Tumors; PR, partial response; SD, stable disease; PD, progressive disease; PFS, progression free survival
8eea62084ca7e541d918e823422bd82e Conclusion
Osimertinib has limited antitumor activity in patients with EGFR exon 20 mutated NSCLC, with an ORR of 6%. A subset of patients (35%) seems to derive benefit from osimertinib treatment with durable disease control for more than five months.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.13-04 - Lorlatinib in Anaplastic Lymphoma Kinase and Proto-Oncogene Tyrosine-Protein Kinase ROS-Positive Non-Small Cell Lung Cancer (ID 14150)
12:00 - 13:30 | Author(s): Robin Cornelissen
- Abstract
Background
In this case series we present ten patients with anaplastic lymphoma kinase (ALK)-rearranged or ROS proto-oncogene 1 (ROS1)-rearranged non-small-cell lung cancer (NSCLC) treated with lorlatinib.
a9ded1e5ce5d75814730bb4caaf49419 Method
Lorlatinib is highly potent and selective third generation ALK and ROS1 tyrosine kinase inhibitor (TKI) with known activity against most resistance mutations. In a phase 1 study, lorlatinib showed intracranial and systemic activity in ROS1-positive and ALK-positive patients with advanced NSCLC.
4c3880bb027f159e801041b1021e88e8 Result
Thus far, we treated 6 ALK- and 4 ROS1-positive stage IV NSCLC patients with lorlatinib in a compassionate use program. Best response was complete remission in two of our patients. One ROS1-positive patient with CNS metastases has now ongoing complete response for 27 months; the other patient with a ALK-positive NSCLC with CNS metastasis has now been treated with lorlatinib for 16 months. Three patients showed a partial response with an ongoing progression free survival of respectively 3, 5 and 8 months. Two of our patients (one ALK-positive and one ROS1-positive NSCLC) showed progressive disease as best response. In three patients response data is not (yet) available. There were no significant side effect apart from hypercholesterolemia, which occurred in four of our patients.
8eea62084ca7e541d918e823422bd82e Conclusion
Lorlatinib shows promise in the treatment of ROS1-positive and ALK-positive patients with advanced NSCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53
