Months For Erlotinib Research Articles

Biological medicines for diffuse intrinsic pontine glioma (DIPG) eradication (BIOMEDE): Final results of an international randomized phase II platform trial comparing 3 targeted therapies in combination with radiotherapy from ITCC, SIOPE-Brain and ANZCHOG.

10003 Background: DIPG is the most aggressive brain cancer in children and adolescents with a median survival of 9 months. Surgery is not possible due to the invasive nature of the disease in a critical area of the brain; only radiotherapy has shown a transient palliative effect on disease progression and no adjuvant therapy has proven to increase disease control. Methods: We launched a large randomized biomarker-driven platform trial to compare three targeted therapies (erlotinib, everolimus and dasatinib) in combination with 54 Gy radiotherapy, in newly diagnosed patients with DIPG (NCT02233049). A central pathological review was performed prior to study entry to confirm the diagnosis of DIPG with H3K27me3 loss (with or without H3K27M mutation) and assess biomarkers. The randomization was designed so that a drug could not be allocated if the corresponding biomarker was absent in the tumor (EGFR overexpression for erlotinib, mTOR activation for everolimus, no specific biomarker for dasatinib). Tumors underwent whole genome sequencing and RNAseq to evaluate prognostic and theranostic biomarkers. Primary endpoint was overall survival. Results: Among the 279 DIPG patients screened for the randomized trial between October 2014 and September 2019, 233 were enrolled in 45 centers in 7 countries; among the 46 screen failures, the diagnosis of DIPG could not be confirmed in 23 patients. No biopsy- or treatment-related death was reported. Serious adverse events > = 3 unrelated to disease progression were reported in 40% of patients, 34%, 36% and 46%, in the erlotinib, everolimus and dasatinib arms, respectively (p = 0.32). With a median follow-up of 5.3 years, median overall survival (OS) from the date of randomization was 9.0 (95% confidence interval, 7.4-14.4), 11.3 (10.3-13.4) and 9.4 (7.7-10.7) months for erlotinib, everolimus and dasatinib, respectively (p = 0.45). OS were not statistically different from those of a historical biopsy-proven cohort. The molecular profiling with copy number aberrations (CNA) had a strong impact on survival (log-rank test, p = 0.0001) as shown by the preliminary analysis of the first hundred patients identifying a group of tumors with very poor prognosis with a HR for death of 1.96 (1.07-3.64) characterized by TP53 mutations (p = 3.05e-11) associated with more CNA (p < 0.0001). Conclusions: This trial demonstrated the feasibility and safety of a large randomized trial for DIPG based on biomarker information from a stereotactic biopsy at diagnosis in an international multicenter setting and generated new tumor biological insights to further develop innovative therapies. Clinical trial information: NCT02233049 .

Real-life effectiveness of first-line anticancer treatments in stage IIIB/IV NSCLC patients: Data from the Czech TULUNG Registry.

BackgroundData regarding real‐life effectiveness of any treatment may improve clinical decision‐making.The aim of this study was to evaluate real‐life effectiveness of tyrosin‐kinase inhibitors, bevacizumab and pemetrexed as first‐line treatments in patients with advanced/metastatic non‐small cell lung cancer (NSCLC).MethodsWe analyzed data of 2157 patients of the Czech TULUNG Registry of patients with advanced/metastatic NSCLC who received modern‐era treatments between 2011 and 2018. Patients treated with gefitinib, erlotinib, afatinib, bevacizumab (+ maintenance), pemetrexed (+ maintenance) as first‐line therapy were included in the study. A systematic literature search separately identified clinical trials suitable for calculation of comparator pooled OS and PFS for each regimen. For each subgroup, basic characteristics and survival data (Kaplan‐Meier estimates) are shown. We propose the “index of real‐life effectiveness” (IRE), a ratio of real‐life OS/PFS and comparator pooled OS/PFS. Univariate and multivariate logistic regression identified factors were associated with longer OS (ie, IRE>1.1).ResultsSurvival analysis showed median OS of 23 months for erlotinib, 29.3 months for afatinib, 19.6 months for gefitinib, 12.2 months for pemetrexed, 17.5 months for pemetrexed maintenance, 15.8 months for bevacizumab and 15.8 months for bevacizumab maintenance. Calculated IREs for OS for the regimens were: erlotinib 1.013, afatinib 1.184, gefitinib 0.736, pemetrexed 1.188, pemetrexed maintenance 1.294, bevacizumab 1.178, and bevacizumab maintenance 1.189. Multivariate regression analysis showed that these factors were associated with longer OS: lower PS for afatinib; lower PS, absence of adverse events and female sex for bevacizumab; and lower PS and female sex for pemetrexed.ConclusionsThis study clearly demonstrated that real‐life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems, and comparison between TULUNG data and pooled survival data from trials showed higher real‐life effectiveness for most of the studied first‐line regimens. Lower ECOG PS, younger age, female sex and adverse events were associated with longer survival in most regimens.Key pointsSignificant findings of the studyComparison between TULUNG data and pooled survival data from trials showed higher real‐life effectiveness for most of the studied first‐line regimens; for most regimens, lower ECOG PS, younger age, female sex and adverse events were associated with longer survival.What this study addsReal‐life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems.

The different central nervous system efficacy among gefitinib, erlotinib and afatinib in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer.

BackgroundBrain metastasis is common in non-small cell lung cancer (NSCLC) and has an even higher incidence in epidermal growth factor receptor (EGFR)-mutant cancers. Although EGFR tyrosine kinase inhibitors (TKIs) are effective against brain metastases, it is unknown which first- or second-generation EGFR TKI is most effective.MethodsPatients treated with first-line gefitinib, erlotinib, or afatinib for advanced EGFR-mutant NSCLC were included. The efficacy against brain metastasis was evaluated by comparing the response rates of measurable and non-irradiated brain metastases, central nervous system progression-free survival (CNS-PFS), and the cumulative incidence of CNS failure.ResultsAmong the 559 patients who received EGFR-TKIs (gefitinib, n=299; erlotinib, n=93; afatinib, n=167), 198 had initial brain metastasis before starting EGFR-TKIs. The CNS response rates of gefitinib, erlotinib, and afatinib were 64.7%, 68.2%, and 72.9%, respectively (P=0.78). In the overall study population, irrespective of initial CNS metastasis, the median CNS-PFS was 17.3 months for gefitinib, 12.4 months for erlotinib, and 23.3 months for afatinib (P<0.001). In multivariate analysis for CNS-PFS, the hazard ratio (HR) of afatinib was 0.63 (95% CI, 0.47–0.83) compared with gefitinib or erlotinib. In the competing risk analysis for cumulative incidence of CNS failure, afatinib showed a lower cumulative incidence of CNS failure compared with gefitinib or erlotinib after adjusting for both EGFR mutation type and preexisting CNS metastases (HR 0.51, 95% CI, 0.34–0.75, P=0.0007).ConclusionsThrough there are some limitation as a retrospective study, afatinib showed similar CNS response rates, superior CNS-PFS and cumulative incidence of CNS failure, compared with gefitinib or erlotinib

OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib versus chemotherapy for the first-line treatment of Asian patients with non-squamous non-small-cell lung cancer

ObjectivesErlotinib, the first generation of epidermoid growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been recommended as an essential treatment in patients with non-small-cell lung cancer (NSCLC) with EGFR mutation. Although...

Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer

Figitumumab (CP-751,871) is a fully human IgG2 monoclonal antibody that inhibits the insulin-like growth factor 1 receptor. This multicenter, randomized, phase III study investigated the efficacy of figitumumab plus erlotinib compared with erlotinib alone in patients with pretreated, nonsmall-cell lung cancer (NSCLC). Patients (stage IIIB/IV or recurrent disease with nonadenocarcinoma histology) who had previously received at least one platinum-based regimen were randomized to receive open-label figitumumab (20 mg/kg) plus erlotinib 150 mg/day or erlotinib alone every 3 weeks. The primary end point was overall survival (OS). Of 583 patients randomized, 579 received treatment. The study was closed early by an independent data safety monitoring committee due to results crossing the prespecified futility boundary. At the final analysis, median OS was 5.7 months for figitumumab plus erlotinib and 6.2 months for erlotinib alone [hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.91-1.31; P = 0.35]. Median progression-free survival was 2.1 months for figitumumab plus erlotinib and 2.6 months for erlotinib alone (HR 1.08; 95% CI 0.90-1.29; P = 0.43). Treatment-related nonfatal serious adverse events occurred in 18% and 5% of patients in the figitumumab arm or erlotinib alone arm, respectively. There were nine treatment-related deaths (three related to both drugs, four related to erlotinib alone and two related to figitumumab). The addition of figitumumab to erlotinib did not improve OS in patients with advanced, pretreated, nonadenocarcinoma NSCLC. Clinical development of figitumumab has been discontinued. NCT00673049.

Maintenance erlotinib in advanced nonsmall cell lung cancer: cost-effectiveness in EGFR wild-type across Europe

BackgroundFirst-line maintenance erlotinib in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) has demonstrated significant overall survival and progression-free survival benefits compared with best supportive care plus placebo, irrespective of epidermal growth factor receptor (EGFR) status (SATURN trial). The cost-effectiveness of first-line maintenance erlotinib in the overall SATURN population has been assessed and published recently, but analyses according to EGFR mutation status have not been performed yet, which was the rationale for assessing the cost-effectiveness of first-line maintenance erlotinib specifically in EGFR wild-type metastatic NSCLC.MethodsThe incremental cost per life-year gained of first-line maintenance erlotinib compared with best supportive care in patients with EGFR wild-type stable metastatic NSCLC was assessed for five European countries (the United Kingdom, Germany, France, Spain, and Italy) with an area-under-the-curve model consisting of three health states (progression-free survival, progressive disease, death). Log-logistic survival functions were fitted to Phase III patient-level data (SATURN) to model progression-free survival and overall survival. The first-line maintenance erlotinib therapy cost (modeled for time to treatment cessation), medication cost in later lines, and cost for the treatment of adverse events were included. Deterministic and probabilistic sensitivity analyses using Monte Carlo simulation (1000 iterations) were performed.ResultsAccording to the model simulations, first-line maintenance erlotinib compared with best supportive care in EGFR wild-type stable metastatic NSCLC resulted in 4.57 months of life gained (17.82 months for erlotinib versus 13.24 months for best supportive care) and 1.14 months of life without progression gained (erlotinib 4.29 versus best supportive care 3.15), and incremental total costs of erlotinib from €7897 (UK) to €9580 (Germany). The corresponding mean incremental cost per life-year gained of erlotinib ranged between €20,711 (UK) and €25,124 (Germany). Sensitivity analyses confirmed these results.ConclusionFirst-line erlotinib maintenance treatment is cost-effective compared with best supportive care in EGFR wild-type stable metastatic NSCLC, irrespective of the country setting.

Sunitinib Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer: A Phase III Trial

Sunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non-small-cell lung cancer (NSCLC), based on the importance of the signaling pathways involved in tumor growth, angiogenesis, and metastasis. This phase III trial investigated overall survival (OS) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC. Patients previously treated with one to two chemotherapy regimens (including one platinum-based regimen) for recurrent NSCLC, and for whom erlotinib was indicated, were randomly assigned (1:1) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d, stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. In all, 960 patients were randomly assigned, and baseline characteristics were balanced. Median OS was 9.0 months for sunitinib plus erlotinib versus 8.5 months for erlotinib alone (hazard ratio [HR], 0.922; 95% CI, 0.797 to 1.067; one-sided stratified log-rank P = .1388). Median PFS was 3.6 months versus 2.0 months (HR, 0.807; 95% CI, 0.695 to 0.937; one-sided stratified log-rank P = .0023), and ORR was 10.6% versus 6.9% (two-sided stratified log-rank P = .0471), respectively. Treatment-related toxicities of grade 3 or higher, including rash/dermatitis, diarrhea, and asthenia/fatigue were more frequent in the sunitinib plus erlotinib arm. In patients with refractory NSCLC, sunitinib plus erlotinib did not improve OS compared with erlotinib alone, but the combination was associated with a statistically significantly longer PFS and greater ORR. The incidence of grade 3 or higher toxicities was greater with combination therapy.

The Qualification of Docetaxel or Erlotinib for Second-Line Therapy Should Be Based on Clinical and Molecular Predictive Factors

Background: We evaluated the effectiveness of docetaxel or erlotinib in second-line treatment of non-small cell lung cancer (NSCLC) and focused on the impact of predictive factors on the outcome of therapy. Methods: 204 patients with progressive disease after platinum-based therapy were enrolled: 102 received an infusion of 75 mg/m² of docetaxel and 102 received 150 mg of erlotinib orally. Results: Response rate (RR) was 6.9 and 8.8% for docetaxel and erlotinib, respectively. Progression-free survival (PFS) was 1.2 months for docetaxel and 1.6 months for erlotinib (hazard ratio, HR = 1.2, p = 0.17). Overall survival was 5.5 versus 7 months for docetaxel and erlotinib, respectively (HR = 1.35, p = 0.06). Using Cox regression, we found clinical factors (performance status and weight loss) with predictive values for RR and PFS in second-line-treated patients. Prior radiotherapy, smoking status and EGFR mutation might help to predict outcome of erlotinib treatment and βIII-tubulin mRNA expression that of docetaxel, but histopathological diagnosis did not have any predictive value. Conclusions: Erlotinib and docetaxel show similar efficacy in the treatment of NSCLC. The application of predictive factors may facilitate qualification for second-line treatment with both drugs.

Phase III Trial of Vandetanib Compared With Erlotinib in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer

Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This phase III study assessed the efficacy of vandetanib versus erlotinib in unselected patients with advanced non-small-cell lung cancer (NSCLC) after treatment failure with one to two prior cytotoxic chemotherapy regimens. One thousand two hundred forty patients were randomly assigned to receive vandetanib 300 mg/d (n = 623) or erlotinib 150 mg/d (n = 617). The primary objective was to show superiority in progression-free survival (PFS) for vandetanib versus erlotinib. If the difference did not reach statistical significance for superiority, a noninferiority analysis was conducted. There was no significant improvement in PFS for patients treated with vandetanib versus erlotinib (hazard ratio [HR], 0.98; 95.22% CI, 0.87 to 1.10; P = .721); median PFS was 2.6 months for vandetanib and 2.0 months for erlotinib. There was also no significant difference for the secondary end points of overall survival (HR, 1.01; P = .830), objective response rate (both 12%), and time to deterioration of symptoms for pain (HR, 0.92; P = .289), dyspnea (HR, 1.07; P = .407), and cough (HR, 0.94; P = .455). Both agents showed equivalent PFS and overall survival in a preplanned noninferiority analysis. Adverse events (AEs; any grade) more frequent with vandetanib than erlotinib included diarrhea (50% v 38%, respectively) and hypertension (16% v 2%, respectively); rash was more frequent with erlotinib than vandetanib (38% v 28%, respectively). The overall incidence of grade ≥ 3 AEs was also higher with vandetanib than erlotinib (50% v 40%, respectively). In patients with previously treated advanced NSCLC, vandetanib showed antitumor activity but did not demonstrate an efficacy advantage compared with erlotinib. There was a higher incidence of some AEs with vandetanib.

New Horizons in Chemotherapy: Platforms for Combinations in First-Line Advanced Non-small Cell Lung Cancer

The treatment of advanced non-small cell lung cancer has evolved substantially during the last decade. Chemotherapy with a platinum-based doublet prolongs survival and improves quality of life in patients with good performance status. Recently, the addition of bevacizumab and the use of epidermal growth factor receptor inhibitors in appropriately selected patients have further improved the outcome of patients with advanced non-small cell lung cancer. Newer targeted agents are being developed and tested in the clinical arena at a rapid pace. In addition, the identification by clinical or molecular criteria of patient populations that benefit the most from these agents is under active investigation. In contrast, the development of newer cytotoxic agents, with innovative mechanisms of action, has been comparatively disappointing. Whether standard cytotoxic drugs are required as newer biologic agents are more frequently used or whether a more active and safer chemotherapy can be used as a template for combinations with biologic agents remains an important research topic.