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Browsing Over 212 Presentations
140P - Prognostic and predictive value of co-mutational profile in advanced EGFR positive NSCLC patients treated with TKIs
- M. Reale (Orbassano, Italy)
- M. Reale (Orbassano, Italy)
- P. Bironzo (Orbassano, Italy)
- L. Righi (Orbassano, Italy)
- A. Listi (Orbassano, Italy)
- F. Tabbò (Orbassano, Italy)
- A. Caglio (Torino, Italy)
- C. Pisano (Orbassano, Italy)
- V. Napoli (Orbassano, Italy)
- M. Di Maio (Torino, Italy)
- S. Novello (Orbassano, Italy)
Abstract
Background
EGFR mutations represent the main model of precision medicine in thoracic oncology. However, an intra-driver diversity exists, explaining heterogeneous clinical behavior and treatment responses.
Methods
We retrospectively analyzed the association between concomitant mutations and outcome of all advanced EGFR+ NSCLC patients treated with tyrosine kinase inhibitors (TKIs) at our Institutions over the last 5 years. We performed next-generation targeted sequencing (Ion Torrent) using a 22 genes clinical panel on diagnostic specimens to analyze the prevalence of co-occurring mutations.
Results
102 patients were evaluated (64% female, 58% never-smokers, 99% adenocarcinoma). Exon 19 deletion, exon 21 L858R, uncommon/double EGFR mutations were present in 62%, 31%, 7%, respectively. Co-mutations occurred in 57 patients (56%), most on TP53 (37, 36%). EGFR exon 19 deletion was associated with a higher incidence of concomitant mutations (39/64, 60.9%) than exon 21 L858R mutation (40.6%, 13/32). Co-mutations had a significantly higher prevalence in younger patients (p = 0.002). RR for patients with and without co-mutations was 63.2% and 51.1% (p = 0.221), respectively. mPFS were 9.93 and 9.64 months in patients with and without co-mutations (HR 0.93, 95% CI 0.59–1.47, p = 0.759), while mOS was 28.7 and 20.8 months (HR 0.74, 95% CI 0.71–1.34, p = 0.319), respectively, with no significant differences according to presence of co-mutations also within treatment subgroups (old vs 3rd generation TKIs). Tumors without co-mutations preferentially progressed to bone and lymph nodes (p = 0.006 and p = 0.027, respectively) with a similar prevalence of T790M resistance mutation at progression (p = 0.72).
Conclusions
We did not demonstrate any significant impact of co-occurring mutations neither on objective response nor on survival in EGFR+ advanced NSCLC treated with TKIs. Co-mutations have higher prevalence in young patients and exon 19 mutated tumors. The growing molecular knowledge has to couple with a careful identification of predictive features in order to lead to a risk-based treatment personalization.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M.L. Reale: Advisory/Consultancy: Eli Lilly. P. Bironzo: Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BeiGene; Advisory/Consultancy: Roche. M. Di Maio: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy: Eisai; Advisory/Consultancy: Janssen; Advisory/Consultancy: Astellas; Research grant/Funding (institution): Tesaro – GlaxoSmithKline. S. Novello: Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
141P - Chemotherapy with or without immunotherapy or bevacizumab for EGFR-mutated lung cancer after progression on osimertinib
- M. White (Stanford, CA, United States of America)
- M. White (Stanford, CA, United States of America)
- J. Neal (Palo Alto, CA, United States of America)
- R. Gardner (Stanford, CA, United States of America)
- K. Cunanan (Stanford, CA, United States of America)
- M. Das (Palo Alto, CA, United States of America)
- S. Padda (Palo Alto, CA, United States of America)
- K. Ramchandran (Palo Alto, CA, United States of America)
- T. Chen (San Jose, United States of America)
- H. Wakelee (Stanford, CA, United States of America)
Abstract
Background
Patients (pts) with advanced EGFR+ lung cancer commonly receive platinum doublet chemotherapy (chemo) regimens after progression on osimertinib (osi), but whether adding immunotherapy (IO) or an anti-angiogenic agent to chemo adds clinical benefit to this group of pts is not well established.
Methods
Pts with advanced EGFR+ lung cancer who had been on osi and went on to receive next-line platinum doublet chemo ± IO ± anti-angiogenic agent before July 6, 2020 were retrospectively identified at our university-affiliated cancer center. Pt demographics, treatment history, and outcomes including time on treatment (TOT) and overall survival (OS) from the start of chemo were collected by chart review. We performed log rank tests to compare difference in TOT and OS distributions between treatment groups.
Results
75 pts were included: 29 received chemo alone, 12 received chemo + IO (pembrolizumab in all cases), and 34 received chemo + anti-angiogenic agent (bevacizumab (bev) in all cases); no pts received chemo with both IO + bev. Median TOT was 3.9 mo (95% CI 1.9–7.8) for chemo alone, 5.2 mo (95% CI 2.5 – Not Estimable) for chemo + IO, and 5.8 mo (4.5 – NE) for chemo + bev; p = 0.17 for between-group differences. Median OS from start of chemo was 12.8 mo (95% CI 6.9–19.5) for chemo, 10.9 mo (95% CI 9.4 – NE) for chemo + IO, and 12.1 mo (95% CI 10.2 – NE) for chemo + bev; p = 0.29 for between-group differences. There were also no differences in TOT or OS in pairwise comparisons between the 3 treatment groups.
| Characteristic | Chemo (n = 29) | Chemo + IO (n = 12) | Chemo + Bev (n = 34) |
|---|---|---|---|
| Median age, years (IQR) | 63.9 (55.3–72.6) | 57.3 (53.4–61.3) | 60.9 (53.2–70.5) |
| Male sex – n (%) | 12 (42) | 6 (50) | 10 (29) |
| Race – n (%) | |||
| Asian | 14 (48) | 6 (50) | 20 (59) |
| White | 11 (38) | 4 (33) | 10 (29) |
| Other | 4 (14) | 2 (17) | 4 (12) |
| ECOG PS – n (%) | |||
| 0–1 | 19 (65) | 11/11 (100) | 29 (85) |
| 2–3 | 10 (34) | 0 | 5 (15) |
| EGFR mutation – n (%) | |||
| Exon 19 deletion | 14 (48) | 7 (58) | 15 (44) |
| L858R | 14 (48) | 5 (42) | 18 (53) |
| Other | 1 (3) | 0 | 1 (3) |
| Received osimertinib in 1st line (vs other EGFR TKIs followed by osi at progression) | 12 (41) | 7 (58) | 13 (38) |
| CNS metastases prior to start of chemo – n (%) | 21 (72) | 6 (50) | 19 (56) |
| Liver metastases prior to start of chemo – n (%) | 9 (31) | 5 (42) | 6 (18) |
Conclusions
After osi therapy, the addition of IO or bev to chemo in pts with EGFR+ lung cancer did not significantly improve clinical outcomes compared with chemo alone in this cohort. Thus, chemo alone seems a reasonable choice for these pts. Future research could examine larger cohorts and adjust for baseline clinical factors. We also await results from ongoing clinical trials examining combinations of chemo ± IO ± bev.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J.W. Neal: Honoraria (self): Research To Practice; Honoraria (self): MLI Peerview; Honoraria (self): Medscape; Honoraria (self): Biomedical Learning Institute; Honoraria (self): Prime Oncology; Honoraria (self): Rockpointe; Honoraria (self): CME Matters; Honoraria (self): MJH CME; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Takeda Pharmaceuticals; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Calithera Biosciences; Advisory/Consultancy: Amgen; Advisory/Consultancy: Iovance Biotherapeutics; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Nektar Therapeutics; Research grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): GlaxoSmithKline; Honoraria (self): UpToDate. R.M. Gardner: Shareholder/Stockholder/Stock options: Pfizer. M. Das: Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): United Therapeutics; Research grant/Funding (institution): Verily; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Varian; Honoraria (self), Advisory/Consultancy: Jazz Pharmaceuticals; Honoraria (self), Advisory/Consultancy: AstraZeneca. S.K. Padda: Research grant/Funding (institution): Epicentrx; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy: Blueprint; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: G1 Therapeutic; Honoraria (self): CME solutions; Advisory/Consultancy: Pfizer; Honoraria (self): PER; Research grant/Funding (institution): 47 Inc.; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Janssen pharmaceuticals; Advisory/Consultancy: Clovis Oncology. K. Ramchandran: Advisory/Consultancy: Dhristi Inc; Advisory/Consultancy: Varian. H. Wakelee: Research grant/Funding (institution): ACEA Biosciences; Research grant/Funding (institution): Arrys Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca/Medimmune; Research grant/Funding (institution): Bristol Myers Squibb; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pharmacyclics; Advisory/Consultancy, Research grant/Funding (institution): Xcovery; Advisory/Consultancy: Janssen; Advisory/Consultancy: Mirati; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Helsinn; Advisory/Consultancy: Blueprint; Honoraria (self): Clinical Care Options Oncology LLC; Honoraria (self): Fishawack Facilitate LTD; Honoraria (self): Medscape; Honoraria (self): Onclive/Intellisphere LLC; Honoraria (self): Physicians Education Resource LLC; Honoraria (self): Prime Oncology LLC; Honoraria (self): Research to Practice; Honoraria (self): UpToDate; Honoraria (self): WebMD Health. All other authors have declared no conflicts of interest.
142P - EGFR-TKI plus Radiotherapy versus EGFR-TKI Only in Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Systematic Review and Meta-Analysis of Observational Studies
- A. Tancherla (Tangerang, Indonesia)
- A. Tancherla (Tangerang, Indonesia)
- F. Wijovi (Tangerang, Indonesia)
- T. Hariyanto (Tangerang, Indonesia)
- A. Kurniawan (Tangerang, Indonesia)
- A. Giselvania (Jakarta, Indonesia)
Abstract
Background
Lung cancer accounts for 25% of all cancer deaths, and 84% are non-small cell lung cancer (NSCLC). The incidence of brain metastasis (BM) was common in NSCLC patients with Epidermal Growth Factor Receptor (EGFR) mutations, reaching a rate of 63%. Some studies have reported the effectiveness of treatment with EGFR-tyrosine kinase inhibitors (TKIs) plus cranial radiotherapy (RT) in NSCLC patients with BM. However, the data available were not consistent. Therefore, we aim to analyse the prognosis and outcome between TKI plus RT versus TKI only in NSCLC patients with BM.
Methods
Data were searched from different databases available online (PubMed, PMC, and Science Direct), using combinations of keywords related to NSCLC patients with BM, RT, and TKI. The included studies evaluated RT and TKI therapy and their association with the survival and response rate in NSCLC patients with BM. Quality of each included study was assessed using the Newcastle-Ottawa Scale (NOS).
Results
A total of 15 cohort studies were included, which consists of five good quality studies and ten moderate quality studies based on NOS. Pooled analysis of the studies had indicated that TKI plus RT was not significantly associated with overall survival (OS), intracranial progression free survival (PFS), and extracranial PFS (p = 0.22, p = 0.20, and p = 0.79 respectively). However, the pooled analysis showed that TKI alone had resulted in superior response rate (RR) when compared with TKI plus RT groups (OR = 1.73, 95% CI; 1.23–2.42; p = 0.002).
Conclusions
Qualitative and quantitative analysis showed that TKI plus RT did not improve the survival of NSCLC patients with BM. This might be due to the observational study design of the included studies which may cause bias and confounding factors. In addition, our study showed that TKI alone resulted in superior RR in comparison with TKI plus RT group. Further randomized clinical trials are needed to evaluate whether the number and size of BM, timing of RT, and different TKI regimens may affect the outcome of the patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
143P - Physician perceptions of barriers to Epidermal Growth Factor Receptor mutation (EGFRm) testing in advanced (stage IIIb / IIIc / IV) Non-Small Cell Lung Cancer (NSCLC)
- J. Subramanian (Kansas City, MO, United States of America)
- J. Subramanian (Kansas City, MO, United States of America)
- Y. Choi (Seoul, Korea, Republic of)
- T. Chou (Taipei, Taiwan)
- J. Gregg (Davis, CA, United States of America)
- R. Hui (Sydney, NS, Australia)
- N. Leighl (Toronto, ON, Canada)
- A. Marchetti (Chieti, Italy)
- N. Navani (London, United Kingdom)
- T. Bailey (Bollington, United Kingdom)
- M. Silvey (Bollington, United Kingdom)
- R. Makin (Bollington, United Kingdom)
- D. Kahangire (Cambridge, United Kingdom)
- M. Chau (Gaithersburg, MD, United States of America)
- A. Taylor (Cambridge, United Kingdom)
- F. Griesinger (Oldenburg, Germany)
Abstract
Background
EGFR mutations are known oncogene drivers in NSCLC. Guidelines recommend EGFRm testing as standard of care in patients with advanced NSCLC. In EGFRm advanced NSCLC patients, EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the preferred first-line treatment. This study investigated real-world EGFR testing and identified barriers to implementation of testing by surveying physicians’ perceptions.
Methods
An online physician survey was conducted in Australia, Canada, Germany, Italy, South Korea, Taiwan, UK and USA (May – Aug 2020). Physicians provided responses on perceptions of EGFR testing patterns, interpretation of results, treatment decisions and attitudes towards testing in advanced NSCLC patients.
Results
Of the 337 physicians included, 82% were Oncologists or Pulmonologists (56% Hospital based, 35% Hospital and office/clinic based, 9% office/clinic based only). Physicians estimated a median 90% of advanced patients are tested for common EGFRm (range 80–100% between countries). Of physicians who reported not always testing for EGFRm, inadequate tissue (47%) and poor performance status (33%) were the main reasons. Physicians estimated a 10 day lapse from biopsy to obtaining results; 26% reported dissatisfaction with delay. Physicians reported testing for EGFR (and PD-L1) prior to selecting treatment in a median 90% of advanced patients. 43% who test prior to selecting treatment indicate at least ‘sometimes’ initiating treatment before receiving results, of whom 57% reported risk of disease progression as the leading factor driving treatment prior to test result. 68% of physicians believed testing delays negatively impact patient outcomes.
Conclusions
Physicians estimated that one in ten advanced NSCLC patients are not tested for EGFR sensitising or activating mutations. Many physicians sometimes initiate treatment prior to receiving test results. Testing delays, sample sufficiency, testing turnaround, performance status and risk of progression may result in treatment initiation, either without EGFR testing or prior to test results, and may result in patients receiving sub-optimal treatment for advanced disease.
Editorial acknowledgement
Medical writing support under the guidance of the authors was provided by Gary Sidgwick of Adelphi Real World, on behalf of Adelphi Real World and AstraZeneca, and was funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
J. Subramanian: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Ely Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Cardinal Health. Y-L. Choi: Research grant/Funding (institution): AstraZeneca. J. Gregg: Shareholder/Stockholder/Stock options, Full/Part-time employment, scope of work at Freenome does not have any COI with data or topic of abstract: Freenome; Speaker Bureau/Expert testimony: AstraZeneca. R. Hui: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy: Ely Lilly; Honoraria (self), Advisory/Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Seagen. N. Leighl: Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca. N. Navani: Honoraria (self): BMS; Honoraria (self): Pfizer; Honoraria (self): Takeda; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Amgen; Advisory/Consultancy: Olympus. D.A. Kahangire: Full/Part-time employment: AstraZeneca. M. Chau: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca; Shareholder/Stockholder/Stock options: Roche. A. Taylor: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. F. Griesinger: Advisory/Consultancy: Roche; Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Takeda; Advisory/Consultancy: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.
144P - Delays in Epidermal Growth Factor Receptor mutation (EGFRm) testing in advanced (stage IIIb / IIIc / IV) Non-Small Cell Lung Cancer (NSCLC) patients and their impact on the use of first line Tyrosine Kinase Inhibitor (TKIs) in a real-world setting
- F. Griesinger (Oldenburg, Germany)
- F. Griesinger (Oldenburg, Germany)
- Y. Choi (Seoul, Korea, Republic of)
- T. Chou (Taipei, Taiwan)
- J. Gregg (Davis, CA, United States of America)
- R. Hui (Sydney, NS, Australia)
- N. Leighl (Toronto, ON, Canada)
- A. Marchetti (Chieti, Italy)
- N. Navani (London, United Kingdom)
- T. Bailey (Bollington, United Kingdom)
- M. Silvey (Bollington, United Kingdom)
- R. Makin (Bollington, United Kingdom)
- D. Kahangire (Cambridge, United Kingdom)
- M. Chau (Gaithersburg, MD, United States of America)
- A. Taylor (Cambridge, United Kingdom)
- J. Subramanian (Kansas City, MO, United States of America)
Abstract
Background
In NSCLC, approximately 10–20% of Caucasian patients and up to 50% of Asian patients harbour EGFRm. Clinical guidelines recommend EGFRm testing as standard of care in advanced NSCLC, with EGFR-TKIs recommended as the optimal first-line (1L) treatment option. This study investigated the real-world use of EGFRm testing and the impact of delays in testing had on disease management.
Methods
A physician survey and chart review conducted in Australia, Canada, Germany, Italy, South Korea, Taiwan, UK and USA (May – Aug 2020) included 223 physicians and provided data on 1,793 advanced NSCLC patients who received a positive first EGFR test result between Jan – Dec 2017. Data on demographics, clinical characteristics, and testing and treatment patterns were abstracted from diagnosis until Mar 2020 (or death).
Results
Median age at diagnosis was 65 years, 54% were male, 17% had a family history of lung cancer. 56% of patients were smokers or ex-smokers, (median pack years: 35); 31% had never smoked. 78% of patients received their EGFR test result ≤2 weeks following test request, while 22% waited >2 weeks. Turnaround times (TAT) varied and were quicker in South Korea (median 7 days) versus Canada (14 days). Longer time from advanced diagnosis to 1L EGFR-TKI initiation was observed in patients with a longer TAT for test result (
| EGFR test turnaround time (weeks) | |||||
|---|---|---|---|---|---|
| Overall (n = 743) | 0–1 (n = 266) | 1–2 (n = 298) | 2–3 (n = 147) | >3 (n = 32) | |
| Median time from advanced diagnosis to 1L EGFR-TKI (weeks) | 4.14 | 2.71 | 4.00 | 5.86 | 8.79 |
Conclusions
A fifth of patients experienced a delay of >2 weeks for EGFR test result, exceeding the recommended ten working day TAT, with notable country differences observed. There was an association between TAT for EGFR test result and initiation of 1L EGFR TKI. Further analysis is required to understand the impact on patient outcomes.
Editorial acknowledgement
Medical writing support under the guidance of the authors was provided by Gary Sidgwick of Adelphi Real World, on behalf of Adelphi Real World and AstraZeneca, and was funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
F. Griesinger: Advisory/Consultancy: Roche; Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Takeda; Advisory/Consultancy: Merck Sharp & Dohme. Y-L. Choi: Research grant/Funding (institution): AstraZeneca. J. Gregg: Shareholder/Stockholder/Stock options, Full/Part-time employment, scope of work at Freenome does not have any COI with data or topic of abstract: Freenome; Speaker Bureau/Expert testimony: AstraZeneca. R. Hui: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy: Ely Lilly; Honoraria (self), Advisory/Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Seagen. N. Leighl: Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca. N. Navani: Honoraria (self): BMS; Honoraria (self): Pfizer; Honoraria (self): Takeda; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Amgen; Advisory/Consultancy: Olympus. D.A. Kahangire: Full/Part-time employment: AstraZeneca. M. Chau: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca; Shareholder/Stockholder/Stock options: Roche. A. Taylor: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. J. Subramanian: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Ely Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Cardinal Health. All other authors have declared no conflicts of interest.
145P - UpSwinG: real-world, non-interventional cohort study on TKI activity in patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC with uncommon mutations
- S. Miura (Niigata, Japan)
- S. Miura (Niigata, Japan)
- T. Hsia (Taichung, Taiwan)
- J. Hung (Kaohsiung, Taiwan)
- H. Jung (Seoul, Korea, Republic of)
- J. Shih (Taipei, Taiwan)
- T. Yang (Taipei, Taiwan)
- C. Park (Hwasun, Korea, Republic of)
- S. Lee (Seoul, Korea, Republic of)
- T. Okamoto (Fukuoka, Japan)
- H. Ahn (Incheon, Korea, Republic of)
- Y. Lee (Jeonju, Korea, Republic of)
- Y. Sato (Hyogo, Japan)
- S. Lee (Busan, Korea, Republic of)
- C. Mascaux (Strasbourg, France)
- H. Daoud (Ingelheim am Rhein, Germany)
- A. Märten (Ingelheim am Rhein, Germany)
- S. Popat (London, United Kingdom)
Abstract
Background
EGFR TKIs are established as an effective treatment (tx) option for pts with EGFRm+ NSCLC with common (Del19 or L858R) mutations, but limited clinical data exist for EGFR TKI use in the 7–23% of NSCLC tumours with uncommon EGFR mutations.
Methods
In this non-interventional, global, multi-centre study (NCT04179890), existing medical or electronic health records were identified for consecutive EGFR TKI-naïve pts with uncommon EGFR mutations treated with either erlotinib, gefitinib, afatinib or osimertinib. Endpoints included time to tx failure (TTF), ORR, OS and duration of response (DoR).
Results
Pts (n = 246; median age: 69.5 yrs; brain metastases: 7%; ECOG PS ≥2: 16%; Asian: 84%) were recruited from 9 countries. Uncommon mutation categories were: major uncommon (G719X, L861Q, S768I; 73%); compound (35%); ex20ins (12%); T790M (7%); other (9%). Most pts (n = 226; 92%) were treated in 1st-line with an EGFR TKI; 132 (54%), 70 (28%), 35 (14%) and 7 (3%) received afatinib, gefitinib, erlotinib and osimertinib. 57% of pts received >1 line of therapy. Mutations were detected using PCR (75%) or sequencing (25%), mainly based on tissue biopsy (86%). Pathology reports varied in quality, often lacking detail on specific mutations, e.g. ‘ex18’ or ‘ex20ins’. Overall, median TTF with an EGFR TKI was 9.9 mos; afatinib: 11.3 mos; gefitinib: 9.2 mos; erlotinib: 8.2 mos. Overall median OS was 24.4 mos. In pts with major uncommon mutations, median TTF was 14.3 and 9.8 mos with afatinib and 1st-gen TKIs. Median TTF in pts receiving 1st-line chemotherapy was only 4.0 mos. ORR was 42% overall (major: 50%; compound: 49%; other: 44%; T790M: 20%; ex20ins: 17%); afatinib: 44% (DoR: 12.0 mos); 1st-gen TKIs: 44% (DoR: 11.0 mos). More detailed analysis will be presented at the conference.
Conclusions
EGFR TKIs were the preferred tx option in pts with uncommon EGFR mutations. Response was highest in pts with major uncommon, and/or compound mutations. Data were in line with recent analyses of afatinib in uncommon mutations. Tx with an EGFR TKI should be considered as standard for pts with uncommon mutations, although many ex20ins were not responsive. To inform optimal tx choice, specific details of EGFR mutations must be reported.
Clinical trial identification
NCT04179890, first posted November 27, 2019.
Editorial acknowledgement
Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Steven Kirkham, of GeoMed, an Ashfield company, part of UDG Healthcare plc, during the development of this abstract.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
S. Miura: Speaker Bureau/Expert testimony: Boehringer Ingelheim Inc.; Speaker Bureau/Expert testimony: MSD Inc.; Speaker Bureau/Expert testimony: Elli Lilly Japan; Speaker Bureau/Expert testimony: Ono Pharma. Inc; Speaker Bureau/Expert testimony: Chugai Pharm Inc. J-Y. Shih: Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Chugai; Honoraria (self): Bristol-Myers Squibb. T. Okamoto: Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Eli Lilly Japan; Honoraria (self): Johnson & Johnson; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Nippon Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Chugai Pharmaceutical; Research grant/Funding (institution): Covidien Japan; Research grant/Funding (institution): Novartis Pharma; Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): Pfizer Japan. H.K. Ahn: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Lilly. Y. Sato: Honoraria (self): Chugai Phama; Honoraria (self): MSD; Honoraria (self): Ono Pharmaceutical CO; Honoraria (self): Novartis; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): AstraZeneca; Honoraria (self): Nippon Kayaku. C. Mascaux: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Kephren; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Pfizer; Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: Takeda. H. Daoud: Full/Part-time employment: Boehringer Ingelheim International GmbH. A. Märten: Full/Part-time employment: Boehringer Ingelheim. S. Popat: Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Roche; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Takeda; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: BMS; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: MSD; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: EMD Serono; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Bayer; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Blueprint; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Guardant Health; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Janssen; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: GSK; Advisory/Consultancy, Consulting fees: BeiGene; Advisory/Consultancy, Consulting fees: Incyte; Advisory/Consultancy, Consulting fees: Eli Lilly; Advisory/Consultancy, Consulting fees: Amgen; Research grant/Funding (institution), Corporate-sponsored research: Ariad; Research grant/Funding (institution), Corporate-sponsored research: Clovis; Research grant/Funding (institution), Corporate-sponsored research: Celgene; Research grant/Funding (institution), Corporate-sponsored research: Epizyme; Research grant/Funding (institution), Corporate-sponsored research: Mirati; Research grant/Funding (institution), Corporate-sponsored research: Trizel; Research grant/Funding (institution), Corporate-sponsored research: Turning Point Therapeutics. All other authors have declared no conflicts of interest.
146P - The impact of prior immune checkpoint inhibitors or osimertinib treatment on NSCLC patients receiving atezolizumab treatment - a real-world observation
- S. Wu (Taipei City, Taiwan)
- S. Wu (Taipei City, Taiwan)
- C. Chiang (Taipei, Taiwan)
- C. Wang (Kaohsiung, Taiwan)
- J. Hung (Kaohsiung, Taiwan)
- T. Hsia (Taichung, Taiwan)
- C. Kuo (Taipei, Taiwan)
- J. Shih (Taipei, Taiwan)
Abstract
Background
Cancer Immunotherapy has become the standard treatment for non-small cell lung cancer (NSCLC) recently. Atezolizumab (atezo) demonstrated survival benefit and has been approved in 1L/2L+ NSCLC. This study aimed to explore the clinical prognostic factors of NSCLC patients receiving atezo-containing regimens in the 2L+ setting.
Methods
We retrospectively collected NSCLC patients who were treated with atezo from 2017 to 2019 in 6 medical centers in Taiwan. Clinical characteristics, treatment course, and responses of patients were recorded.
Results
There were 128 NSCLC patients who have received 2L+ atezo, including 38 (30%) patients in 2L and 90 (70%) in 3L+ setting. The outcomes of atezo-containing regimens were response rate 10.2%, median progression-free survival (mPFS) 3.5 (95% confidence interval [CI]: 2.9–4.1) months, and median overall survival (mOS) 10.7 (95% CI: 9.4–12.0) months. Thirteen of 128 (10%) patients with prior immune checkpoint inhibitors (ICIs) treatment before atezo-containing regimens had shorter mPFS (2.4 months versus 3.5 months; p = 0.009) and mOS (5.4 months versus 12.0 months; p < 0.001) than those without prior ICIs treatment. Multivariate analysis of the prognostic factors for survival revealed that prior ICIs treatment (hazard ratio [HR]: 2.61; p = 0.003) and poor performance status (HR: 3.17; p < 0.001) were associated with poor prognosis. In addition, there were 34 patients with EGFR-mutant non-squamous NSCLC who had received EGFR-TKIs before atezo treatment, including 9 patients who have been treated with osimertinib. The patients with osimertinib treatment before atezo had shorter mPFS (2.8 months versus 4.8 months; p = 0.010) and mOS (12.0 months versus 5.4 months; p < 0.001) than those without osimertinib treatment. Multivariate analysis also revealed an association of shorter OS with osimertinib treatment before atezo (HR: 5.49; 95% CI: 1.76–17.14; p = 0.003).
Conclusions
ICIs and osimertinib treatment before atezolizumab treatment were poor prognostic factors in NSCLC patients. Further studies with larger sample sizes are needed to validate this observation.
Legal entity responsible for the study
This study was managed by Formosa Biomedical Technology Corp. contract research organization and overseen by Roche Products Ltd., Taiwan.
Funding
This study was sponsored by Roche Products Ltd.
Disclosure
S-G. Wu: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer. C-L. Chiang: Honoraria (self): Roche; Honoraria (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca. T-C. Hsia: Research grant/Funding (self): Eli Lilly. J-Y. Shih: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Chugai Pharmaceutical; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Novartis. All other authors have declared no conflicts of interest.
147P - PD-L1 expression influenced by osimertinib treatment in advanced EGFR T790M-positive non-small cell lung cancer patients
- Y. Yu (Shanghai, China)
- Y. Yu (Shanghai, China)
- L. Xia (Shanghai, China)
- J. Zhou (Hangzhou, China)
- K. Wang (Hangzhou, China)
- Y. Zhang (Hangzhou, China)
- C. Zhang (Huhhot, China)
- A. Liu (Nanchang, China)
- Y. Fan (Hangzhou, China)
- J. Chang (Shanghai, China)
- L. Wang (Nanjing, China)
- Y. Liu (Shenyang, China)
- S. Lu (Shanghai, China)
Abstract
Background
Anti-PD-1/L1 antibodies could be an optional therapy for EGFR-TKI-resistant non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, little is known about PD-L1 expression in advanced NSCLC patients with the T790M-positive EGFR mutation, as well as the changes induced by osimertinib treatment.
Methods
From July 2017 to February 2020, 63 advanced NSCLC patients with T790M-positive EGFR mutation were screened and enrolled in the study to receive osimertinib treatment at 80 mg orally once daily. PD-L1 expression on tumor cells at baseline and after progression was evaluated by immunohistochemistry with VENTANA PD-L1 (SP263) assay.
Results
The mean age of the 63 enrolled patients was 61.4±10.77 years, including 29 males (46.0%) and 34 females (54.0%). All patients were Chinese and most of them were advanced NSCLC patients with adenocarcinoma (60/63, 95.2%). The osimertinib treatment duration and follow-up time ranged from 6 to 126 weeks. At baseline, the positive rate of PD-L1 expression on tumor cells with different cut-off points (≥1%, ≥25%, ≥50%) was 34.1% (14/41), 4.9% (2/41), and 4.9% (2/41), respectively. After progression, among 12 samples tested for PD-L1 expression, 41.7% (5/12), 16.7% (2/12) and 8.3% (1/12) were PD-L1 positive on tumor cells with cut-off points at 1%, 25% and 50%, respectively. Ten patients with samples tested both at baseline and after progression were analyzed for the change of PD-L1 expression. The mean change in the positive rate of PD-L1 expression from baseline to progression was 9.05% (95% CI: -4.895%, -22.995%, P = 0.0625, n = 10). Among these 10 patients, PD-L1 expression on tumor cells were all negative (< 1%) at baseline, but 50%≥5/10, ≥ 1% expression), 20%≥2/10, ≥25%) and 10%≥1/10, ≥50%≥of them were positive after progression.
Conclusions
We observed that PD-L1 expression on tumor cells tended to increase after osimertinib treatment in advanced EGFR T790M-positive NSCLC patients, which may provide clues for optimization of subsequent anti-PD-1/L1 treatment. The effect of osimertinib treatment on PD-L1 expression in EGFR T790M-positive NSCLC patients warrants further validation in study with a larger population.
Legal entity responsible for the study
Guangdong Association of Clinical Trails (GACT) Chinese Thoracic Oncology Group (CTONG).
Funding
AstraZeneca.
Disclosure
All authors have declared no conflicts of interest.
148P - Neutrophil to Lymphocyte Ratio as a Prognostic Factors in Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Treated with Tyrosine Kinase Inhibitor: A Systematic Review and Meta-Analysis
- R. Heriyanto (Tangerang, Indonesia)
- R. Heriyanto (Tangerang, Indonesia)
- J. Tandiono (Tangerang, Indonesia)
- E. Marcella (Tangerang, Indonesia)
- B. Susanto (Tangerang, Indonesia)
- S. Chen (Tangerang, Indonesia)
- F. Wijovi (Tangerang, Indonesia)
- A. Tancherla (Tangerang, Indonesia)
- A. Kurniawan (Tangerang, Indonesia)
Abstract
Background
Recent studies have shown the prognostic value of pre-treatment NLR in advanced cancers; However, the role of NLR in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitor (TKI) remains unclear. Thus, this study aims to investigate the association between pre-treatment NLR with outcomes in EGFR-mutant NSCLC patients.
Methods
We searched data from PMC, PubMed, Google Scholar, Science Direct, and Scopus, on January 5th, 2021 using a combination of keywords associated with advanced NSCLC with EGFR mutation, treatment using TKI, and neutrophil-lymphocyte ratio in relation to their outcome. Publications included are limited to English manuscripts that were published in the past 10 years, and exclusion criteria are NSCLC patients without EGFR mutation and not treated with TKI. All studies are reviewed and evaluated by all 7 authors. The quality of each included study was assessed using the Newcastle-Ottawa Scale (NOS) and GRADE.
Results
A total of 10 retrospective studies consisting of 1532 EGFR mutated NSCLC patients treated with TKI were included. All 10 included study were of good quality, based on GRADE this study is moderate in quality as there are minimal inconsistency and variability in results and there are no publication biases. 9 studies showed that higher pre-treatment NLR is associated with significantly worse OS and PFS. 1 study showed that in patients treated with TKI, NLR is not a significant prognostic factor of OS, nor PFS. Pooled analysis showed that high NLR is significantly associated with worse OS and PFS (HR = 1.65; 95% CI, 1.18–2–31; p < 0.00001, HR = 1.52; 95% CI, 1.16–1.99; p < 0.00001) when compared with those with low NLR.
Conclusions
Current studies demonstrated that high pre-treatment NLR is significantly associated with worse OS and PFS compared to low pre-treatment NLR, making it a promising biomarker for the prognosis of EGFR mutated NSCLC patients treated with TKI, which warrants further prospective investigation.
Legal entity responsible for the study
Rivaldo Steven Heriyanto.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
149P - First line (1L) osimertinib in EGFR mutant (mut) advanced non-small-cell lung cancer (aNSCLC) patients (pts): progression (PD) pattern and safety in the real-world (RW)
- M. Lorenzi (Padua, Italy)
- M. Lorenzi (Padua, Italy)
- A. Dal Maso (Padova, Italy)
- A. Ferro (Padova, Italy)
- V. Polo (Treviso, Italy)
- D. Scattolin (Padua, Italy)
- M. Macerelli (Udine, Italy)
- A. Follador (Udine, Italy)
- G. Targato (Udine, Italy)
- S. Indraccolo (Padova, Italy)
- S. Frega (Padova, Italy)
- J. Menis (Padova, Italy)
- L. Bonanno (Padova, Italy)
- V. Guarneri (Padova, Italy)
- P. Conte (Padova, Italy)
- G. Pasello (Padova, Italy)
Abstract
Background
RW data on PD pattern and safety of 1L osimertinib in EGFR mut aNSCLC are currently lacking.
Methods
This is an observational, multicenter study enrolling EGFR mut aNSCLC receiving 1L osimertinib between November 2018 and 2020. Primary endpoints were treatment outcomes: median progression free survival (mPFS), time to treatment failure (mTTF) and PD patterns. Safety profile was also recorded as a secondary endpoint. PD was classified as isolated (single lesion PD), oligoprogression (oligoPD; PD in ≤ 3 lesions in ≤ 2 sites), systemic all others.
Results
At data cut-off (January 5, 2021), 82 pts receiving osimertinib were included in 3 centres: 52 (63.4%) were female, 46 (56.1%) never smokers. Baseline EGFR mutations were exon 19 deletion in 39 (47.6%) pts, L858R in 36 (43.9%) pts, others in 7 (8.6%) pts. ECOG performance status was 0–1 in 65 (79.3%) pts. Number (N) of metastatic sites at diagnosis was <3 in 52 (63.4%) pts, ≥ 3 in 30 (35.6%) pts; 27 (32.9%) pts had brain metastases. Median follow-up was 11.2 months (mo). Response rate was 68.3%, disease control rate 86.6%. mPFS was 22.0 mo (95%CI, 11.4–32.5), mTTF 25.3 mo (95%CI, 18.9-not calculable). PD was reported in 28 (34%) pts; median N of PD sites was 2 (range 1–7); the most frequent PD sites were lung (N = 19, 67.9%), bone (N = 11, 39.3%) and brain (N = 7, 25%). New PD sites were present in 11 (39.3%) pts; median N = 1 (range 1–4). Isolated PD was observed in 5 (17.9%) pts, oligoPD in 6 (24.4%) and systemic in 16 (57.1%). 9 cases underwent tissue and/or liquid rebiopsy at PD. Druggable resistance mechanisms were identified in 5 pts: MET amplification (amp) (N = 3), MET amp/EGFR amp (N = 1) and HER2 amp (N = 1). The most frequent any grade (G) adverse events (AEs) were diarrhea (N = 33, 40.2%), rash (N = 32, 39.0%), paronychia (N = 22, 26.8%) and creatinine increase (N = 25, 30.5%). The most frequent G3/4 AEs were thromboembolic events (N = 6, 7.3%), diarrhea (N = 4, 4.9%), arterial thromboembolism (N = 2, 2.4%) and rash (N = 2, 2.4%).
Conclusions
Osimertinib confirmed efficacy and safety in RW. Thromboembolic events were observed more frequently than previously reported. The study is still ongoing in order to recruit a larger patient population.
Legal entity responsible for the study
Veneto Institute of Oncology IOV – IRCCS.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
150P - A phase I study of TQ-B2450, a PD-L1 mAb, plus anlotinib in EGFR+ advanced NSCLC patients failed to prior EGFR TKI therapies
- J. Feng (Nanjing, China)
- J. Feng (Nanjing, China)
- M. Shi (Nanjing, China)
- L. Wang (Nanjing, China)
- S. Yu (Nanjing, China)
- F. Yan (Nanjing, China)
- W. Peng (Nanjing, China)
Abstract
Background
Platinum-based chemotherapy is the standard therapy for the patients(pts) with EGFR-mutation-positive advanced NSCLC failed to prior EGFR TKI therapies. However, the IMpower150 study subgroup analyses show Atezolizumab (PD-L1) plus bevacizumab and chemotherapy improved overall survival in EGFR TKI treated NSCLC. TQ-B2450 is a humanized PD-L1 mAb, anlotinib, an antiangiogenic multi-target TKI. This ongoing phase I study aimed to assess the safety and effect of TQ-B2450 plus anlotinib in EGFR+ advanced NSCLC pts failed to prior EGFR TKI therapies.
Methods
Pts with EGFR+ advanced NSCLC who failed to prior EGFR TKI therapies were eligible. Pts with previous received platinum-based chemotherapy were excluded. Anlotinib was given orally for 2 weeks of a 21-day cycle (days 1–14), with TQ-B2450 given at 1200 mg every 3 weeks on day 1. A standard 3+3 dose escalation design was used to evaluate various doses of anlotinib in combination with TQ-B2450 to determine the RP2D. Secondary endpoints were ORR, DCR and PFS.
Results
From 11/2019–6/2020, 9 pts were enrolled. During anlotinib dose-escalation, pts received doses of 8 mg (n = 3), 10 mg (n = 3) and 12 mg (n = 3). No DLTs were observed. The most common grade 1–2 adverse events (AEs) included Hand and foot skin reaction (33.3%) and proteinuria (22.2%). Only two Grade 3 AEs which was hypertension. Among 9 evaluable pts, DCR was 77.8% (7/9) and the other 2 pts had disease progression, the median PFS was 9.1 months (95% CI [4.2. 9.3]).
Conclusions
TQ-B2450 plus anlotinib was well tolerated with evidence of clinical activity. Based on dose exploration, 12 mg is the RP2D. Further evaluation is warranted for pts with EGFR+ advanced NSCLC who failed to prior EGFR TKI therapies.
Clinical trial identification
ChiCTR1900026273.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
151P - Osimertinib versus Standard-of-care EGFR-TKI as First-line Treatment for Advanced NSCLC with EGFR-positive Mutation Patients: A Systematic Review
- S. Chen (Tangerang, Indonesia)
- S. Chen (Tangerang, Indonesia)
- E. Marcella (Tangerang, Indonesia)
- B. Susanto (Tangerang, Indonesia)
- J. Tandiono (Tangerang, Indonesia)
- R. Heriyanto (Tangerang, Indonesia)
- F. Wijovi (Tangerang, Indonesia)
- A. Tancherla (Tangerang, Indonesia)
- A. Kurniawan (Tangerang, Indonesia)
Abstract
Background
Brain metastases are a very common complication in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-positive mutation. The existence of the blood-brain barrier makes it difficult for chemotherapeutic agents with poor penetrability to work. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKIs), is reported to have better penetration ability and potency compared to the standard-of-care EGFR TKIs (gefitinib and erlotinib). This study investigates the efficacy of osimertinib compared to other EGFR TKIs.
Methods
On January 4th 2021, data was collected from PMC, PubMed, Google Scholar, Science Direct, and Scopus, using a combination of keywords associated with advanced NSCLC and treatment using EGFR TKI in relation to their efficacy. Included publications were limited to those published in the last 10 years with English manuscripts and were all reviewed and evaluated by the authors. All included studies are clinical trials with an inclusion criteria of adult (≥18 years old) patients with untreated NSCLC with EGFR-positive mutation, and exclusion criteria of any patients with brain metastases who were neurologically unstable. The quality of each studies was assessed using the Newcastle-Ottawa Scale (NOS) and all included studies were good in quality according to the NOS.
Results
All 5 studies with a total of 998 patients claimed that osimertinib showed efficacy superior to the standard EGFR TKIs used in the first-line treatment of advanced EGFR mutation-positive NSCLC. One study specified that although osimertinib is superior in terms of efficacy, key symptom improvements did not favour any of the EGFR TKIs.
Conclusions
Osimertinib is proven to be superior in terms of efficacy compared to gefitinib and erlotinib, the standard-of-care EGFR TKIs. It also has a similar safety profile despite a longer duration of exposure and therefore should be considered for first-line therapy in advanced NSCLC patients who are EGFR-mutation positive.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.