Abstract 2982
Background
Alflutinib (AST2818) is an irreversible EGFR-TKI selective for EGFR T790M mutation. We aimed to assess the safety and efficacy of alflutinib in advanced non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation, who progressed after the first- or second-generation EGFR-TKI therapy.
Methods
In the phase I/II open-label, single-arm, dose-escalation and dose-expansion studies, patients with confirmed EGFR T790M mutation, locally advanced or metastatic NSCLC, who progressed after prior EGFR-TKI therapy, received alflutinib ranging from 20 - 240 mg orally once daily until disease progression or unacceptable toxicity. Patients with asymptomatic, stable central nervous system (CNS) metastases were included. The primary efficacy endpoint was the objective response rate (ORR), assessed by independent radiological review committee, in patients who received at least 1 dose with measurable disease at baseline in the dose-expansion study. Safety was assessed in all treated patients.
Results
Between Dec 27, 2016, and Oct 30, 2018, 130 (14 from dose-escalation, 116 from dose-expansion) patients received alflutinib treatment (2, 9, 48, 53, 18 patients in 20, 40, 80, 160 and 240 mg groups, respectively). By Oct 30, 2018, 79 (61%) patients remained on treatment. No dose limiting toxicity was observed. Median duration of alflutinib treatment was 226 (range: 3 - 513) days. The ORR in all treated patients was 76.7% (89/116; 95% CI: 68.0 - 84.1), duration of response ranged from 72 - 294+ days, disease control rate was 82.8% (96/116 patients). The ORR in patients with CNS metastases was 58.8% (10/17). No clear dose-response relationship was observed. Among 130 patients, 123 (95%) had treatment-related adverse events (TRAEs, including possibly not-related cases); 21 (16%) patients had grade 3 or 4 TRAEs, with the most common being decreased neutrophil count (4 patients). 20 (15%) patients had 31 serious adverse events (SAEs), 15 (12%) of them had 22 treatment-related SAEs. Five out of six deaths were due to AEs.
Conclusions
Alflutinib has promising efficacy and acceptable toxicity profile for NSCLC patients with EGFR T790M mutation who progressed after EGFR-TKI therapy. Further investigation is ongoing.
Clinical trial identification
NCT02973763, NCT03127449.
Editorial acknowledgement
Ping Liu (Linking Truth Technology Co. Ltd., China), funded by Shanghai Allist Pharmaceuticals Inc., China.
Legal entity responsible for the study
Shanghai Allist Pharmaceuticals Inc., China.
Funding
Shanghai Allist Pharmaceuticals Inc., China.
Disclosure
Y. Jiang: Full / Part-time employment: Shanghai Allist Pharmaceuticals Inc., China. All other authors have declared no conflicts of interest.
Resources from the same session
3345 - Escalation plans and DNACPR discussions in the unwell oncology patient
Presenter: Raghad Elghadi
Session: Poster Display session 1
Resources:
Abstract
4165 - The Relation between the Symptom Burden of Hospitalized Patients with Incurable Cancer and the Quality-of-Life of Their Family Caregivers
Presenter: Eman Tawfik
Session: Poster Display session 1
Resources:
Abstract
1784 - Clinical predictors for analgesic response to radiotherapy in patients with painful bone metastases
Presenter: Ragnhild Habberstad
Session: Poster Display session 1
Resources:
Abstract
5323 - 30-Day Mortality in Palliative Radiotherapy
Presenter: Shing Fung Lee
Session: Poster Display session 1
Resources:
Abstract
3942 - The relationship between Naldemedine administration and the maximum dose of oral opioids
Presenter: Shinya Kajiura
Session: Poster Display session 1
Resources:
Abstract
3698 - Exposure to low energy amplitude modulated radiofrequency electromagnetic fields (EMF) is associated with rapid improvement in quality of life (QoL) status in patients with advanced hepatocellular carcinoma (HCC), using various analyses of EORTC-C30.
Presenter: Elizabeth Santana
Session: Poster Display session 1
Resources:
Abstract
3885 - Olanzapine Combined with 5-HT3 RA Plus Dexamethasone for Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting in High and Moderate Emetogenic Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Presenter: Jian-Guo Zhou
Session: Poster Display session 1
Resources:
Abstract
5700 - Early Palliative care in advanced cancer, is it really effective?
Presenter: Raquel Gómez Bravo
Session: Poster Display session 1
Resources:
Abstract
5924 - Deprescribing Potentially Inappropriate Medication in Cancer Patients
Presenter: Simon Reuter
Session: Poster Display session 1
Resources:
Abstract
5314 - Spirituality and religious coping for Cancer patients and providers: An ‘Almighty’ belief for palliative care
Presenter: Vibhay Pareek
Session: Poster Display session 1
Resources:
Abstract