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Inger Johanne Zwicky Eide
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-035 - Osimertinib in Relapsed EGFR-Mutated Non-Small Cell Lung Cancer Patients with Brain Metastases: Results from the TREM-Study (ID 9286)
09:30 - 09:30 | Presenting Author(s): Inger Johanne Zwicky Eide
- Abstract
Background:
Osimertinib, an irreversible EGFR-TKI with activity also against the resistance mutation T790M, has a high brain permeability surmising intracerebral efficacy in T790M-negative cases. We assessed the efficacy of osimertinib in T790M-positive and –negative patients.
Method:
The TREM-study is an investigator initiated phase 2, single-arm, multi-center clinical trial conducted in five Northern European countries. Patients with advanced EGFR-mutated NSCLC with progression after at least one EGFR-TKI were assigned to treatment with osimertinib 80 mg daily until radiological progression or death. Both T790M-positive and –negative patients were enrolled, as well as patients with stable and asymptomatic brain metastases. The primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints were progression free survival (PFS), duration of response (DoR), disease control rate (DCR) and overall survival (OS). We here present data from a subset of patients with brain metastases at study entry.
Result:
Of 147 included patients, 34 presented with CNS-metastases at inclusion. This subset of patients had poorer performance status at baseline than the full study cohort (31 % with ECOG 2 in the CNS-subgroup vs 17 % in the full study cohort) and the median age was lower (61.5 vs 65 years), otherwise similar to the full cohort in terms of baseline characteristics. 69 % (20/29) were T790M-positive and 31 % (9/29) negative. 5 patients had unknown T790M-status. 28 patients were evaluable for response. ORR was 39 % (11/28) and DCR 75 % (21/28). For T790M-positive patients ORR was 53 % (9/17) and DCR 88 % (15/17), in T790M-negatives 13 % (1/8) and 38 % (3/8) respectively. Median DoR in T790M-positive patients was 14.7 months (95 % CI 6.4-22.9) and 5.5 months in one T790M-negative patient. Two patients had ongoing responses after 15.9 and 17.5 months at data cutoff. Median PFS in the CNS-subgroup was 7.2 months (95 % CI 4.1-10.3 months) vs 9.7 months (6.3-13.1) in patients without CNS metastases, p=0.300, regardless of T790M-status. In the CNS-subgroup PFS in the T790M-positive patients was 10.1 months (7.9-12.3) vs 2.0 months (0.9-3.2) in the T790M-negative patients, p<0.001. Of 18 patients who had progressed at cutoff, 7 had CNS as site of progression (4 T790M-negative, 2 unknown and only one T790M-positive).
Conclusion:
Although a limited number of patients in this subgroup analysis, our results show that osimertinib has similar efficacy in patients with CNS disease as without, whereas the benefit in T790M-negative patients may be substantially lower.
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P2.03-037 - Osimertinib in Relapsed EGFR-Mutated, T790M-Negative Non-Small Cell Lung Cancer (NSCLC) Patients: Results from the TREM-Study (ID 9415)
09:30 - 09:30 | Presenting Author(s): Inger Johanne Zwicky Eide
- Abstract
Background:
The resistance mutation T790M emerges in around 60 % of EGFR-TKI treated NSCLC patients. Osimertinib is approved only in T790M-positive patients. We assessed the efficacy of osimertinib in both T790M-positive and -negative patients and here present results from T790M-negative patients.
Method:
In this investigator initiated, multicenter, single-arm, phase 2 clinical trial conducted in five Northern European countries, patients with progression on at least one previous EGFR-TKI and with measurable disease by RECIST 1.1 were assigned to treatment with 80 mg of osimertinib daily until radiological progression or death. Rebiopsy for assessment of mutational status was done after inclusion. Plasma samples were collected for translational research purposes (not analyzed yet). The primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints were progression free survival (PFS), duration of response (DoR), disease control rate (DCR) and overall survival (OS).
Result:
T790M-status was assessable in rebiopsies from 120 of 147 included patients. Of these, 42 patients (35 %) were T790M-negative in tissue. 55 % (23/42) of the T790M-negative patients had exon 19 deletion at diagnosis as opposed to 71 % of the T790M-positives, other baseline factors were similar between the two groups. ORR in the T790M-negative group was 19 % (7/36) including one patient with complete response. In the T790M-positive group, ORR was 52 % (37/71), no complete responses. DCR was 64 % (23/36) and 87 % (62/71), respectively. All responses were confirmed. Median DoR was 11.0 months (95 % CI 3.0-19.1) in the negatives and 12.0 months (8.7-15.2) in the positives, p = 0.887. In the T790M-negative group, median PFS was 5.5 months (2.6-8.3) vs 10.8 months (8.2-13.4) in the T790M-positive group, p = 0.009. Subgroup analyses were performed in the T790M-negative group and there was significant higher median PFS in patients without CNS-metastases (5.6 vs 1.6 months, p = 0.007), in patients with duration of previous TKI-treatment over median (15 months) vs under (9.7 vs 3.5 months, p = 0.044) and in patients with one previous line of TKI vs two or more lines (7.3 vs 2.0 months, p = 0.007).
Conclusion:
T790M-negative patients who respond have similar DoR as T790M-positive patients. T790M-negative patients without CNS-metastases and with durable response on first EGFR-TKI could benefit from osimertinib.
