Advanced EGFR-mutated Non-small Cell Research Articles

Safety and efficacy of osimertinib plus consolidative stereotactic ablative radiation (SABR) in advanced EGFR mutant non-small cell lung cancer (NSCLC): Results from a multi-center phase II trial.

8518 Background: Despite high response rates to EGFR inhibitors, patients with advanced EGFR mutant NSCLC generally experience disease progression within two years (osimertinib median PFS 18.9 months, median OS 38.6 months). We sought to determine whether administration of SABR to residual sites of disease at the time of expected best response to EGFR inhibition could prolong disease control. Methods: This was a multi-center single-arm phase 2 study. Eligible patients had advanced EGFR mutant (exon 19 or 21) NSCLC not restricted by number, site, or size of metastases; ECOG 0-2; no prior treatment with EGFR inhibitors or immune checkpoint inhibitors; and no history of interstitial lung disease. Patients with stable or responding disease after 8 weeks of osimertinib received SABR to persisting lesions, followed by continued osimertinib until progression or intolerance. At subsequent progression, patients could receive further SABR and continue osimertinib if deemed clinically feasible and appropriate. The primary endpoint was progression-free survival (PFS); secondary endpoints included duration on osimertinib, toxicity, and overall survival (OS). Results: A total of 43 patients (32 women, 11 men) were enrolled and initiated osimertinib, of whom 29 (67%) received SABR. Reasons SABR was not administered included inadequate response (9%), insufficient residual disease (19%), and other (5%). At a median follow-up of 35.7 months (95% CI, 28.8, 37.6), 42 evaluable patients had a median PFS of 32.6 months and a median OS of 45.7 months. The median duration of osimertinib was 31.5 months. Grade ≥3 toxicities included one incidence each (2%) of the following: pain at the site of radiation, paronychia, liver enzyme elevation, fatigue, hyponatremia, diarrhea, and pneumonitis. Conclusions: Osimertinib plus consolidative SABR appears to provide a PFS and OS benefit when considered against historical data with osimertinib alone. This treatment strategy may offer a well-tolerated and practical approach to improving outcomes for patients with advanced EGFR mutant NSCLC. Clinical trial information: NCT03667820 .

HSR24-124: Determinants of Quality of Life and Optimism in Patients With EGFR Mutated Advanced Non-Small Cell Lung Cancer.

HSR24-124: Determinants of Quality of Life and Optimism in Patients With EGFR Mutated Advanced Non-Small Cell Lung Cancer.

EP12.01-10 Predictors of Poor Outcomes Among Patients Receiving 1st-Line Osimertinib for Advanced EGFR Mutated Non-Small Cell Lung Cancer

EP12.01-10 Predictors of Poor Outcomes Among Patients Receiving 1st-Line Osimertinib for Advanced EGFR Mutated Non-Small Cell Lung Cancer

Circulating tumor DNA to guide furmonertinib monotherapy or combination therapy in advanced EGFR mutant non-small cell lung cancer (NSCLC): A randomized, open-label, multicenter study (FOCUS-C).

TPS9150 Background: Detection of EGFR ctDNA after several weeks EGFR-TKIs treatment was an effective method to identify prognosis of advanced EGFR mutant NSCLC patients. Patients with uncleared EGFR ctDNA had shorter progression-free survival (PFS) ( Mack PC et al; CCR 2022). However, whether they can benefit from EGFR-TKI combination therapy has not been reported. Furmonertinib (AST2818), a potent, orally bioavailable, highly brain penetrant, third generation EGFR-TKI with unique chemical structure designed to improve potency and specificity, showed superior efficacy compared with gefitinib as first-line therapy in EGFR mutant NSCLC along with an acceptable safety profile without new signals ( Shi, YK et al.; Lancet Respir Med 2022). We hypothesized that monitoring clearance of EGFR ctDNA in blood could rationally guide subsequent monotherapy or combination therapy with furmonertinib and will improve outcomes in patients with uncleared EGFR ctDNA. Methods: The FOCUS-C study is a multicenter, open-label, randomized study. Patients who are aged 18 years or older and have histologically confirmed, locally advanced or metastatic, stage IIIB, IIIC, or IV unresectable NSCLC with EGFR exon 19 deletions (19Del) or exon 21 Leu858Arg mutation (L858R) on tissue biopsy and plasma will be treated with furmonertinib. Eligible patients with uncleared EGFR 19Del or L858R ctDNA after 3 weeks furmonertinib treatment will be stratified according to EGFR mutation (19Del or L858R), central nervous system metastases (with or without) and detectable accompanying gene aberrances in plasma (with or without) and randomly assigned (2: 2: 1) to receive furmonertinib or furmonertinib plus chemotherapy (pemetrexed and carboplatin for 4 cycles followed by maintenance pemetrexed) or furmonertinib plus chemotherapy plus bevacizumab (pemetrexed, carboplatin and bevacizumab for 4 cycles followed by maintenance pemetrexed and bevacizumab) in 21-day cycles until disease progression, the occurrence of intolerable toxicities, withdrawal of consent, or other discontinuation reasons judged by the investigators. The primary endpoint is PFS between furmoneritnib plus chemotherapy versus furmonertinib alone. Secondary endpoints include PFS, objective response rate, duration of response, disease control rate, overall survival and safety. Several exploratory endpoints will also be evaluated based on ctDNA detection by next-generation sequencing (Genecast, Wuxi, China). The study is enrolling. 34 patients had been enrolled till 2nd Feb 2023. Clinical trial information: NCT05334277 .

Efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors combined with chemotherapy as first-line treatment for epidermal growth factor receptor-mutant advanced non-small cell lung cancer

Objective: To observe the clinical efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with chemotherapy as first-line treatment for EGFR mutant advanced non-small cell lung cancer (NSCLC). Methods: It was a retrospective, single-arm real-world study and a total of 39 patients with stage ⅢB to Ⅳ EGFR mutant NSCLC diagnosed in Cancer Hospital of Chinese Academy of Medical Sciences from July 2018 to December 2020 were collected. There were 16 males and 23 females, the age ranged from 25 to 73 years, with a median age of 53 years. All patients received EGFR-TKIs synchronously combined with pemetrexed and platinum-containing chemotherapy for 4-6 cycles as first-line treatment, followed by EGFR-TKI monotherapy with or without pemetrexed maintenance therapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and adverse reactions were evaluated. Median follow-up time was 18.6 months (95%CI: 16.2-21.0 months). The Kaplan-Meier method was used for survival analysis. Results: The ORR was 61.5% (24/39), the DCR was 94.9% (37/39) and the median PFS was 16.4 months (95%CI: 12.1-20.7 months). The main adverse reactions were liver function injury (59.0%, 23/39), myelosuppression (43.6%, 17/39), skin reaction (25.6%, 10/39), gastrointestinal reaction (17.9%, 7/39), fatigue (12.8%, 5/39) and kidney injury (5.1%, 2/39). Most of the patients had grade 1-2 adverse reactions, and the rate of grade 3 adverse events were 12.8%(5/39), which were effectively alleviated after symptomatic support treatment, no grade 4 serious adverse events occurred. Conclusion: EGFR-TKIs synchronously combined with chemotherapy followed by EGFR-TKI monotherapy with or without pemetrexed maintenance therapy has a certain therapeutic effect and fairly good safety, which can prolong PFS in patients with EGFR mutated advanced NSCLC.

EP08.02-074 Impact of Germline BRCA1/2 Alterations on EGFR Mutant Advanced Non-small Cell Lung Cancer Outcomes

Incidental pathogenic germline variants (iPGV) in BRCA1/2 may be identified in patients with advanced non-small cell lung cancer (aNSCLC) by somatic genotyping via tissue or plasma-based assays. However, impact of iPGVs on patient outcomes is not well understood. Because of the sensitivity of BRCA-deficient cancers to various therapies, it is of interest to understand the impact of these iPGVs on molecularly homogenous lung cancer population. Using real-world evidence (RWE), we aimed to explore the impact of iPGV findings in BRCA1/2 (gBRCA), identified by a well-validated liquid biopsy assay, on outcomes in patients with aNSCLC who received EGFR targeted therapy.

Diagnostic-Therapeutic Pathway and Outcomes of Early Stage NSCLC: a Focus on EGFR Testing in the Real-World.

BackgroundOsimertinib is considered the standard-of-care for previously-untreated EGFR mutant advanced non-small cell lung cancer (NSCLC). Oncogene driver screening in early NSCLC is not standard practice. A real-world study has been designed in order to investigate the optimal testing frequency and timing for EGFR mutations in early NSCLC in clinical practice.Patients and MethodsThe present observational, retrospective study evaluated the real-world diagnostic-therapeutic pathway and clinical outcomes of 225 patients with stage I-III NSCLC, with particular reference to the EGFR-mutant subgroup.ResultsPrior to surgery, 101 patients had undergone a diagnostic biopsy; EGFR mutational analysis was available in 56 (55%) patients and 12 patients (21%) had a cancer harboring an EGFR mutation. Among surgical specimens, reflex EGFR test was performed in 181 (80%) of 225 and 35 cases (19%) were EGFR mutant. The majority of patients had not received adjuvant chemotherapy (N=174, 77%) or adjuvant radiotherapy (N=201, 89%). Of 49 (22%) patients experiencing disease relapse, 26 (53%) received first-line systemic treatment. All EGFR-mutant relapsed patients (N=6, 12.2%) received an EGFR-TKI. Median overall survival (OS) and relapse-free survival for the entire population were not reached. Multivariate analysis for OS confirmed a significant correlation with age, female gender, EGFR status, necrosis score, perineural invasion, and relapsed disease. EGFR test costs represented 1.6-2.4% of the total costs of management per patient (€34,340).ConclusionsOur results suggest that the frequency of EGFR mutations in early stage (I-III) NSCLC is similar to that of advanced stages. Reflex EGFR testing in all early-stage NSCLC at diagnosis or after surgery appears to be a valid tool to give patients the chance to benefit from targeted adjuvant treatment.

A phase II study of osimertinib in combination with platinum plus pemetrexed in patients with EGFR-mutated, advanced non–small cell lung cancer: The OPAL study (NEJ032C/LOGIK1801).

9097 Background: Osimertinib (OSI), a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI), is now a standard treatment for previously untreated EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC). In the two randomized phase 3 studies, progression-free survival (PFS) and overall survival were statistically significant and clinically longer with gefitinib and platinum-based chemotherapy compared with gefitinib monotherapy. Based on these data, we have planned this phase 2 study to evaluate the safety and efficacy of OSI combined with platinum-based chemotherapy. Patients and Methods: This multicenter phase 2 study enrolled patients (pts) with clinical stage IIIB, IIIC, IVA, IVB or postoperative recurrent, previously untreated EGFRm NSCLC. Pts received oral OSI 80mg once daily (QD), with either cisplatin 75mg/m2 (arm A) or carboplatin [area under the curve (AUC) = 5, arm B], plus pemetrexed (PEM) 500 mg/ m2 every 3 weeks (Q3W) for four cycles. In both arms, maintenance was OSI 80mg QD with PEM 500 mg/ m2 Q3W until disease progression or discontinuation. The co-primary endpoints were the safety and the objective response rate (ORR), and the secondary endpoints included the complete response rate (CRR), disease control rate (DCR), and PFS. Results: From July 2019 to February 2020, 67 pts (34 pts in Arm A; 33 pts in arm B) were enrolled: median (range) age 67 (26-75) years; 43 (64.2%) female; 46 (68.7%) ECOG PS 0; 66 (98.5%) adenocarcinoma; 31 (46.3%) EGFR exon19 deletion, 35 (52.2) L858R, and 1 (1.5%) both. One pt did not comply with the eligibility criteria and was excluded from the efficacy analysis. At data cut off (August 31, 2021), 27 (40.3%) pts [15 (44.1%) in arm A and 12 (36.4%) in arm B] had discontinued the protocol treatment, including 9 (13.4%) pts [5 (14.7%) in arm A and 4 (12.1%) in arm B] due to the adverse event (AE). The rate of grade (G) ≥ 3 AEs were 91.0% (88.2% in arm A and 93.9% in arm B). For the safety, neutropenia, anemia and thromobocytopenia were numerically higher in arm B and the rates of G ≥ 3 were 29.4%/60.6%, 14.7%/27.3% and 0.0%/42.4% in arm A/B, respectively. G ≥ 3 QTc interval prolonged and G ≥ 2 anorexia were observed in 14.7%/21.2% and 26.5%/24.2%, respectively. For the efficacy, the ORR was 90.9% [95% confidence interval (CI); 84.0-97.8%]. The CRR/DCR were 3.0%/97.0% (95% CI; 0.0-7.2%/92.8%-100.0%), respectively. At a median follow-up time of 21.4 months (range, 18.2-25.7), median PFS was not reached in both A and B, with an estimated 12-/24-months PFS rate of 90.4%/70.0%. Conclusions: OSI combined with platinum-based chemotherapy for previously untreated EGFRm advanced NSCLC showed the excellent efficacy with tolerable toxicity. This combination treatment is highly promising and should be validated in the phase 3 study. Clinical trial information: jRCTs031180226.

Utility of Next-Generation Sequencing in the Reconstruction of Clonal Architecture in a Patient with an EGFR Mutated Advanced Non-Small Cell Lung Cancer: A Case Report

EGFR tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, targeted therapies impose a strong selective pressure against the coexisting tumor populations that lead to the emergence of resistant clones. Molecular characterization of the disease is essential for the clinical management of the patient, both at diagnosis and after progression. Next-generation sequencing (NGS) has been established as a technique capable of providing clinically useful molecular profiling of the disease in tissue samples and in non-invasive liquid biopsy samples (LB). Here, we describe a case report of a patient with metastatic NSCLC harboring EGFR mutation who developed two independent resistance mechanisms (EGFR-T790M and TP53 + RB1 mutations) to dacomitinib. Osimertinib given as a second-line treatment eliminated the EGFR-T790M population and simultaneously consolidated the proliferation of the TP53 + RB1 clone that eventually led to the histologic transformation to small-cell lung cancer (SCLC). Comprehensive NGS profiling revealed the presence of the TP53 + RB1 clone in the pretreatment biopsy, while EGFR-T790M was only detected after progression on dacomitinib. Implementation of NGS studies in routine molecular diagnosis of tissue and LB samples provides a more comprehensive view of the clonal architecture of the disease in order to guide therapeutic decision-making.

Observation on Effect of Gefitinib Combined with Gemcitabine and Cisplatin in the Treatment of Elderly Patients with Advanced EGFR Mutant Non-small Cell Lung Cancer

Observation on Effect of Gefitinib Combined with Gemcitabine and Cisplatin in the Treatment of Elderly Patients with Advanced EGFR Mutant Non-small Cell Lung Cancer

1398P Real-life progression (PD) pattern of EGFR mutant advanced non-small cell lung cancer (aNSCLC) patients (pts) receiving systemic therapy after first- or second-generation tyrosine kinase inhibitor (1-2 gen TKI)

1398P Real-life progression (PD) pattern of EGFR mutant advanced non-small cell lung cancer (aNSCLC) patients (pts) receiving systemic therapy after first- or second-generation tyrosine kinase inhibitor (1-2 gen TKI)

Role of Anti-EGFR Targeted Therapies in Stage III Locally Advanced Non-small Cell Lung Cancer: Give or Not to Give?

Identification of targetable mutations such as EGFR has allowed opportunity for Tyrosine Kinase Inhibitor (TKI) therapy for lung cancer treatment. EGFR-TKIs have revolutionized treatment of advanced EGFR mutant Non-Small Cell Lung Cancer (NSCLC), but there is little evidence that EGFR-TKI treatment is effective in stage III NSCLC. Here we discuss recent evidence supporting the use of EGFR-TKI therapy in combination with chemotherapy and radiation in stage III NSCLC. Recent results of small trials testing EGFR-TKI therapy in combination with chemoradiation showed promising efficacy, improved outcomes, and a tolerable toxicity profile when administered to patients with EGFR mutant stage III NSCLC. However, strong supporting evidence regarding EGFR-TKI therapy in stage III NSCLC is lacking because previous trials involved a small patient population or were terminated due to slow participant accrual. Despite the lack of large randomized clinical trials, results from early-stage trials highlight promising future directions for investigating the use of EGFR-TKI therapy in stage III NSCLC treatment.

Prognostic value of quantitative measurement of EGFR mutation using peptide nucleic acid clamping in advanced EGFR mutant non-small cell lung cancer patients.

BackgroundThe presence of EGFR mutation in patients with advanced non‐small cell lung cancer (NSCLC) plays an important role in determining the appropriate treatment, response, and survival. Therefore, this study attempted to predict the prognosis of NSCLC patients using data from quantitative mutation measurements.MethodsThe data of patients with advanced NSCLC who underwent EGFR mutation testing using the peptide nucleic acid (PNA) mediated clamping method at the Pusan National University Hospital from October 2015 to December 2017 were retrospectively analyzed. The efficiency of PNA clamping was determined by measuring the threshold cycle (Ct) value. The ΔCt−1 value (standard Ct value minus sample Ct value) was calculated to quantify EGFR mutation.ResultsDuring the study period, 71 patients were treated with EGFR‐tyrosine kinase inhibitors. The cutoff point for the ΔCt−1 value derived from the receiver operating characteristic curve was 5.32. A survival benefit was observed in the group with an ΔCt−1 value > 5.32 or with a common EGFR mutation type compared to the group with an ΔCt−1 value < 5.32.Conclusion EGFR mutation testing using PNA clamping may predict patient survival, especially in patients with common EGFR mutations, such as exon 19 deletion or L858R. A higher ΔCt−1 value correlates with better survival.

Phase III randomized trial comparing gefitinib to gefitinib with pemetrexed-carboplatin chemotherapy in patients with advanced untreated EGFR mutant non-small cell lung cancer (gef vs gef+C).

9001 Background: Standard first-line therapy for EGFR mutant advanced non-small cell lung cancer (NSCLC) is an EGFR-directed oral TKI. We evaluated whether adding pemetrexed-carboplatin to oral TKI would improve outcomes. Methods: Phase III randomized trial in advanced chemotherapy-naïve NSCLC harboring EGFR sensitizing mutation (exon 19, 21 or 18) with performance status (PS) 0 to 2 planned for palliative therapy. Patients were stratified for PS and EGFR mutation and randomly assigned (computer-generated randomization by independent biostatistician) 1:1 to gefitinib 250 mg orally daily (gef) or gefitinib 250 mg orally daily with pemetrexed 500 mg/m2 IV and carboplatin AUC 5 IV every 3 weeks for 4 cycles, followed by maintenance pemetrexed 500 mg/m2 IV every 3 weeks (gef+C). Restaging was every 2 to 3 mths; therapy continued until progression or intolerable toxicity. Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), toxicity and response rate. Survival endpoints were assessed in the intention-to-treat population. Results: Between Aug 2016 and Aug 2018, 350 patients were randomly assigned to gef (n = 177) and gef+C (n = 173). Median age was 54 yrs, 48% were females, 84% never-smokers, 21% were PS 2 and 18% had brain metastases. Median follow-up in surviving patients was 17 months (range, 7 to 30). Radiologic response rates were 81% and 69% in gef+C and gef respectively, P = 0.012. 234 patients (67%) have had events for PFS, 98 in gef+C and 136 in gef. Estimated median PFS was significantly longer with gef+C than gef (16 months, [95% CI, 13.7 to 18.3] vs. 8 months [95% CI, 7.1 to 8.9]; hazard ratio for disease progression or death, 0.5; 95% CI, 0.39 to 0.65; P &lt; 0.001). 120 patients (34%) have died, 42 in gef+C and 78 in gef. Estimated median OS was significantly longer with gef+C than gef (not reached vs. 18 months [95% CI, 14.28 to 21.72]; hazard ratio for death, 0.45; 95% CI, 0.31 to 0.66; P &lt; 0.001). Clinically relevant ≥ grade 3 toxicities occurred in 51% and 25% of patients in gef+C and gef arms respectively, P &lt; 0.001. Conclusion: Adding pemetrexed-carboplatin chemotherapy to gefitinib significantly prolonged progression free and overall survival but also increased toxicity. Pemetrexed-carboplatin-gefitinib represents a new standard first-line therapy for EGFR mutant NSCLC. Clinical trial information: CTRI/2016/08/007149.

Influence of afatinib dose on outcomes of advanced EGFR-mutant NSCLC patients with brain metastases

BackgroundAfatinib is an oral irreversible epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) indicated in first-line treatment of advanced EGFR-mutant (EGFRm+) non-small cell lung cancer (NSCLC). Dose dependent side effects can limit drug exposure, which may impact on extracranial and central nervous system (CNS) disease control.MethodsWe performed a retrospective study of 125 patients diagnosed with advanced EGFRm+ NSCLC treated with first-line afatinib at a tertiary Asian cancer center, exploring clinicopathological factors that may influence survival outcomes. Median progression free survival (PFS) was estimated using the Kaplan-Meier method. Comparison of PFS between subgroups of patients was done using log-rank tests and Cox proportional hazards models.ResultsOut of 125 patients, 62 (49.6%) started on 40 mg once daily (OD) afatinib, 61 (48.8%) on 30 mg OD and 1 (0.8%) on 20 mg OD. After median follow-up of 13.8 months from afatinib initiation, the observed response rate was 70.4% and median PFS 11.9 months (95% CI 10.3–19.3). 42 (33.6%) patients had baseline brain metastases (BM) and PFS of those who started on 40 mg OD (n = 17) vs. 30 mg OD (n = 25) was 13.3 months vs. 5.3 months (HR 0.39, 95% CI 0.15–0.99). BM+ patients who started on 40 mg had similar PFS to patients with no BM (13.3 months vs. 15.0 months; HR 0.79, 95% CI 0.34–1.80).ConclusionIn patients with advanced EGFRm+ NSCLC with BM+, initiating patients on afatinib 40 mg OD was associated with improved PFS compared to 30 mg OD, underscoring the potential importance of dose intensity in control of CNS disease.

P3.15-21 Real-World Experience of First-Line Afatinib Treatment in Patients with EGFR Mutant Advanced Non-Small Cell Lung Cancer

Background: Published reports of first-line afatinib treatment efficacy, side-effects and resistance mechanism in the real-world setting are lacking. Method: A retrospective observational study of patients with EGFR mutant advanced non-small cell lung cancer (NSCLC) receiving first-line afatinib in University Malaya Medical Center from 1st December 2014 to 30th April 2018. Result: Twenty-two of 33 patients on first-line afatinib were eligible for analysis. The patients’ demographic and clinical characteristics are as shown in Table 1. The mPFS was 14.3 months, overall response rate was 86.3% (19/22) and disease control rate was 95.5% (21/22). The median time-to-treatment failure was 16.2 months. The median overall survival has not been reached but 12-month survival rate was 81.8% (18/22). A patient with exon 18 G719X and exon 20 S768I mutation had received treatment for 23.3 months without disease progression (PD). The PFS of a patient with exon 20 insertion was 9 months and of another patient with exon 18 G719X and exon 20 T790M mutations was 4.4 months. Of patients with brain metastases, the PFS of 2 patients treated with stereotactic radiosurgery (SRS) was 15.9 months and 9 months, respectively while that of a patient who had whole brain radiotherapy (WBRT) and a patient who underwent debulking surgery only was 16.5 months and 2.6 months, respectively. The incidence of side-effects was rash 90.1% (20/22), stomatitis 63.3% (14/22), paronychia 72.7% (16/22), and diarrhea 77.3% (17/22). One (4.5%) patient each had grade 3 diarrhea and cutaneous lesions. Of 17 patients with PD, 2 (11.8%) had PD in the brain. T790M mutation was detected in 62.2% (8/13) patients who underwent repeat biopsy. Conclusion: Afatinib is an effective treatment of EGFR-mutant advanced NSCLC. When combined with SRS or WBRT, afatinib conferred good PFS in patients with symptomatic brain metastases. Severe side effects are uncommon and T790M mutation was the commonest resistance mechanism.

P1.01-109 Phase I Study of Apatinib Plus Gefitinib as First-Line Therapy in Patients with EGFR Mutant Advanced Non-Small Cell Lung Cancer

P1.01-109 Phase I Study of Apatinib Plus Gefitinib as First-Line Therapy in Patients with EGFR Mutant Advanced Non-Small Cell Lung Cancer

P3.13-15 First-Line Afatinib Dose Initiation and Adjustment in Patients with EGFR Mutant Advanced Non-Small Cell Lung Cancer

Background: The recommended starting dose of afatinib is 40mg od with 20mg, 30mg and 50mg tablets available for dose adjustment. Method: This is a retrospective observational study of starting dose, dose adjustment and optimal dose of first-line afatinib in patients withEGFR mutant advanced non-small cell lung cancer in University Malaya Medical Center from 1st December 2014 to 30th April 2018. Result: Of 22 patients on first-line afatinib, the starting dose was 40 mg od in 12 patients and 30 mg od in 10 patients (Figure 1). Among the 12 patients started on afatinib 40mg od, 4 (33.3%) did not require dose adjustment, 4 (33.3%) needed dose reduction to 30mg od, 2 (16.7%) needed dose reduction to 20mg od, and 2 (16.7%) had dose escalation to 50mg od. Among 10 patients started on afatinib 30mg od, 6 (60%) did not require dose adjustment, 1 (10%) needed dose reduction to 25mg od and 3 (30%) had dose escalation to 40mg od. Dose reduction was to reduce the cost of treatment in 1 patient and to reduce drug related side-effects in the rest. Dose escalation was exclusively to improve disease control. The overall response rate and disease control rate was 80% (8/10) and 90% (9/10) in patients who did not require dose adjustment; while the respective rates were 85.7% (6/7) and 100% (7/7) in patients who had dose reduction. The optimal dose of afatinib defined by good disease control and tolerable side-effects was 50mg od in 9.1% (2/22), 40mg od in 31.8% (7/22), 30mg od in 31.8% (7/22), 25mg od in 13.6% (3/22) and 20mg od in 13.6% (3/22) of patients. Conclusion: We suggest starting afatinib at 30mg od and adjust the dose accordingly because dose adjustment is not required in most cases on this starting dose and it is the commonest optimal dose.

1444P - A randomized phase II trial of erlotinib or erlotinib and bevacizumab in patients with advanced EGFR mutant non-small cell lung cancer (NSCLC)

1444P - A randomized phase II trial of erlotinib or erlotinib and bevacizumab in patients with advanced EGFR mutant non-small cell lung cancer (NSCLC)

Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer

BackgroundLUX-Lung 3 showed afatinib improved progression-free survival (PFS) compared with cisplatin plus pemetrexed in patients with epidermal growth factor receptor (EGFR) mutations. In this study, chemotherapy efficacy tended to differ between patients with Leu858Arg (L858R) point mutation and Exon 19 deletion (Del-19); PFS in L858R patients (8.1 months) was greater than in Del-19 patients (5.6 months). We investigated whether there is any difference in efficacy of cisplatin plus pemetrexed between Del-19 and L858R.MethodsThis study is a multicenter retrospective study. We reviewed medical records of patients who had received cisplatin plus pemetrexed as first line chemotherapy. Efficacies were evaluated between EGFR mutation status: Del-19 and L858R. Wild type cases were reference arm only, and not included in any statistical analysis.ResultsAmong 304 patients, 78 (25.7%) harbored EGFR mutations: Del-19 (36/78 patients, 46.2%); and L858R (42/78, 53.8%). Median PFS of L858R group (9.4 months, 95% confidence interval [CI]: 7.0–12.6) was significantly longer than Del-19 group (5.5 months, 95% CI, 3.6–8.6) (p = 0.049). Response rate (RR) and OS presented no significant difference between L858R and Del-19. In multivariate analysis, EGFR mutation status (L858R versus Del-19) was the only significant factor for longer PFS (Hazard ratio [HR]: 0.78, 95% CI: 0.62–0.98) (p = 0.033).ConclusionOur study indicated better efficacy of cisplatin plus pemetrexed in L858R than in Del-19 patients. In EGFR-mutant NSCLC, EGFR-TKIs are undoubtedly the premier therapy. However, in second line or later settings, cisplatin plus pemetrexed regimen may confer higher efficacy for L858R patients.