Maintenance Erlotinib Research Articles

99P Bevacizumab plus erlotinib maintenance versus observation in advanced biliary tract cancers: Results from the phase II component of a prospective integrated phase II-phase III parallel design superiority clinical trial (BEER-BTC study)

99P Bevacizumab plus erlotinib maintenance versus observation in advanced biliary tract cancers: Results from the phase II component of a prospective integrated phase II-phase III parallel design superiority clinical trial (BEER-BTC study)

Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) versus intercalated TKI with chemotherapy for EGFR-mutated nonsmall cell lung cancer.

IntroductionPrevious studies have shown interference between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy in the cell cycle, thus reducing efficacy. In this randomised controlled trial we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR-mutated nonsmall cell lung cancer (NSCLC).Materials and methodsTreatment-naïve patients with an activating EGFR mutation, ECOG performance score of 0–3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2–16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival, objective response rate (ORR) and toxicity.ResultsBetween April 2014 and September 2016, 22 patients were randomised equally into both arms; the study was stopped due to slow accrual. Median follow-up was 64 months. Median PFS was 13.7 months (95% CI 5.2–18.8) for CPE and 10.3 months (95% CI 7.1–15.5; hazard ratio (HR) 0.62, 95% CI 0.25–1.57) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.24, 95% CI 0.07–0.83; p=0.02). ORR was 64% for CPE versus 55% for erlotinib monotherapy. Median overall survival was 31.7 months (95% CI 21.8–61.9 months) for CPE compared to 17.2 months (95% CI 11.5–45.5 months) for erlotinib monotherapy (HR 0.58, 95% CI 0.22–1.41 months). Patients treated with CPE had higher rates of treatment-related fatigue, anorexia, weight loss and renal toxicity.ConclusionIntercalating erlotinib with cisplatin-pemetrexed provides a longer PFS compared to erlotinib alone in EGFR-mutated NSCLC at the expense of more toxicity.

Induction EGFR tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage III EGFR-mutated non-small cell lung cancer

IntroductionIncreasing evidence suggests that consolidation durvalumab confers limited benefits for patients with stage III EGFR-mutated NSCLC. Induction or maintenance EGFR tyrosine kinase inhibitors (TKIs) added to concurrent chemoradiotherapy (CRT) may optimize definitive treatment, but there are limited data supporting an induction TKI strategy. MethodsWe evaluated the efficacy and safety of induction EGFR TKIs administered before concurrent CRT in a retrospective series of patients with unresectable locally advanced EGFR-mutated NSCLC. Circulating tumor DNA (ctDNA) analysis was performed on a patient subset using CAPP-seq and correlated with outcomes. ResultsOf six patients, three received erlotinib and three osimertinib as induction therapy before CRT. Induction TKIs were administered for a median of 2.5 months. The objective response rate after induction TKI was 83%. One patient had a complete response to induction erlotinib and continued erlotinib for 4 years until local progression, which was treated with CRT. Two patients completed maintenance erlotinib after CRT, and another received consolidation durvalumab. After a median follow-up of 20.5 months, only one patient developed disease recurrence, with rising ctDNA coinciding with recurrence. ctDNA remained undetectable in patients without recurrence, or low-level in a patient receiving maintenance erlotinib. Adverse events were mild and expected, and none developed pneumonitis. ConclusionInduction EGFR TKI before CRT may achieve high disease control rates with promising signs of durability in patients with locally advanced EGFR-mutated NSCLC. ctDNA analysis after CRT can correlate well with clinical outcomes. Prospective studies are needed to define the role of induction EGFR TKIs in this setting.

Deep learning-based predictive imaging biomarker model for EGFR mutation status in non-small cell lung cancer from CT imaging.

3106 Background: Deep learning based radiogenomic (DLR) models present a promising performance in assisting lung cancer care. The purpose of this study was 1) To develop and validate DLR signatures to predict the EGFR mutation, 2) To assess the incremental value of these DLR signatures in comparison to the traditional clinical and semantic features. Methods: 223 patients were selected from two phase III randomized trials in patients with advanced non-squamous NSCLC with EGFR-sensitizing mutation and EGFR wild type who were planned to receive palliative therapy (trial 1: gefitinib or gefitinib plus pemetrexed and carboplatin and trial 2: pemetrexed maintenance and erlotinib maintenance). Our method is an end-to-end pipeline that requires only the manually selected tumour region in a CT image without precise tumour boundary segmentation or human-defined features. Two deep convolutional neural networks with 3D U-Net architectures are trained to segment lung masses and nodules from 3D regions of the CT image. The primary end point was EGFR prediction using Radiomics and DLR pipeline. We also compared the performance of combination of models in predicting the mutational status. Results: A total of 223 patients (mean age, 54.18 years; age range, 28–80 years) were included in this study. There were 121 (54.3%) patients with EGFR mutation and 102 (45.7%) patients who were EGFR wild type. On multivariate logistic regression analysis, Clinical variable and CT semantic features that were found to be significantly associated EGFR mutation were tumor stage, smoking status, pure solid texture, presence of non-tumor lobe nodule, and average enhancement. For predicting EGFR mutation, ROC curve plotted with clinical variables model, CT semantic variables model, Radiomics model, DLR model showed an AUC value of 0.70, 0.73, 0.94, 0.72 respectively. Clinical variables and semantic features were added to the radiomics predictive model and deep learning predictive model independently, showed further improvement in the accuracy for either model from AUC 0.94+/-0.02 to 0.96+/-0.02 and from AUC 0.72+/-0.02 to 0.82+/-0.04 respectively. Conclusions: The radiomics and DLR model by machine-learned information, extracted from CT images without precise manual segmentation, could predict EGFR mutation with very high accuracy. This AI based model can be used as non-invasive and easy-to-use surrogate imaging biomarker for EGFR mutation status prediction. Clinical trial information: CTRI/2018/10/022102 .

Leptomeningeal metastasis from non-small cell lung cancer- outcomes from a tertiary care center.

e14508 Background: Leptomeningeal metastasis from Non-Small Cell Lung Cancer is often an underdiagnosed entity. Despite advances in treatment, the outcomes of Leptomeningeal Metastasis continues to be dismal. The data on outcomes of leptomeningeal metastasis from a tertiary care centre is limited. Methods: Data collected from the 4 prospective randomised controlled trials conducted on Non Small cell Lung cancer patients at our centre in the last decade was used in the analysis. These included 1. Patients who had EGFR sensitizing mutations enrolled in the Pemetrexed versus Gefitinib maintenance trial and Gefitinib versus Gefitinib plus chemotherapy trial. 2. Patients who were diagnosed as Squamous Cell Carcinoma of lung enrolled in the Low Dose Gemcitabine versus Standard-Dose Gemcitabine trial. 3. Patients with adenocarcinoma who were enrolled in the Pemetrexed versus Erlotinib maintenance trial. We separated the patients who developed Leptomeningeal Metastasis from these trials and studied its incidence, presenting features and outcomes. Statistical analysis was done using cox regression analysis and kaplan meier plots. Results: Out of 1148 patients, 36 patients (0.031%; 95%CI 0.022-0.043) developed leptomeningeal metastasis. In these patients, the median time to development of LM was 14.92 months (IQR 7.7-21.84). The median overall survival after development of LM was 61 days (95%CI 38.95-83.05). None of the tested factors- Age (Hazard ratio-0.886; 95% CI 0.424-1.851, P-value = 0.747), ECOG PS (Hazard ratio-0.719; 95%CI 0.299-1.729) or driver mutation status ( Hazard ratio-2.080, 95%CI 0.739-5.855) had an impact on OS. The median OS in driver mutated patients was 66 days (95% CI 14.74-117.26) versus 51 days (95% CI 14.5-87.5) (P-value = 0.201). Conclusions: In our study, there was no single factor which impacted survival in patients who developed Leptomeningeal Metastasis. The median survival was in the range of 2 months. This reiterates the overall poor prognosis of development of Leptomeningeal Metastasis in Non small Cell Lung Cancer even with the development of newer therapeutic modalities. Keywords- Leptomeningeal metastasis, Non small cell lung cancer, Incidence, Survival.

Randomized phase 3 open label study of quality of life of patients on Pemetrexed versus Erlotinib as maintenance therapy for advanced non squamous non EGFR mutated non small cell lung cancer.

Background: We planned to compare pemetrexed maintenance with erlotinib maintenance in non squamous non Epidermal Growth Factor Receptor (EGFR) mutated non small cell lung cancer (NSCLC). The null hypothesis for this study was that there would be no difference in quality of life (QOL) between pemetrexed and erlotinib maintenance. Results: The QL2 scores at 3 months were 63.35 (SD 24.99) in pemetrexed arm and 63.01(SD 23.04) in erlotinib arm (p-0.793). Except in 1 domain, the scores were statistically similar between the 2 arms. In the domain of diarrhea, the score was higher as expected in the erlotinib arm (p-0.048). The median progression free survival was 4.5 months (95%CI 4.1–4.9 months) in pemetrexed arm versus 4.5 months (95%CI 3.8–5.2 months) in erlotinib arm (p-0.94). The median overall survival was 16.6 months (15.2–17.9 months) in pemetrexed arm versus 18.3 months (95% CI 13.75–22.91 months) in erlotinib arm (p-0.49). Methods: The study was an open label, single centre, parallel, phase 3 randomized study with 1:1 randomization between maintenance pemetrexed arm and erlotinib arm. Adult patients (age > or = 18 years), with non squamous EGFR mutation, treated with first line palliative therapy, with non progressive disease post 4–6 cycles of pemetrexed-carboplatin were randomized. Primary outcome was change in the score of QOL (Global health status {QL2}) at 3 months. We estimated that with 200 patients, the study had 80% power to detect a significant difference between the two groups in the change in the global health status score at 3 months with an alpha error of 5%, with an effect size of 0.3 SD. Conclusions: Maintenance pemetrexed post pemetrexed-platinum chemotherapy fails to improve QOL or time to event outcomes over maintenance erlotinib in EGFR mutation negative NSCLC.

Transformation to small cell lung cancer and activation of KRAS during long-term erlotinib maintenance in a patient with non-small cell lung cancer: A case report.

Epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (non-SCLC) benefits from first-line treatment with first generation tyrosine kinase inhibitors (TKIs). However, drug resistance is inevitable through different mechanisms and is dominated by the acquisition of the T790M mutation within EGFR, which occurs in ~50% of cases. The present study reports the case of a patient originally diagnosed with stage IA lung adenocarcinoma, with a recurrent tumor lesion in each side of the lungs following the surgical removal of the primary tumor. Erlotinib treatment of the recurrent tumors eliminated the tumor on the right side of the lung and resulted in the histological transformation of the tumor on the left side to SCLC following 6 years of treatment. Genetic profiling of the SCLC lesions using targeted next-generation sequencing identified different genetic alterations from the primary tumor, characterized by the newly acquired copy number loss of tumor protein p53 and transcriptional coreceptor 1, and the copy number gain of SRY-box 2. Continuation of treatment with chemotherapy and erlotinib demonstrated moderate disease control for ~1 year prior to the outbreak of a new lung lesion. Liquid biopsy profiling of circulating tumor DNA revealed the acquisition of KRAS proto-oncogene, GTPase (KRAS) p.G12C mutation, indicating the occurrence of another resistance mechanism to erlotinib. During erlotinib treatment, the lung adenocarcinoma progressed through two atypical mechanisms, notably from the transformation to SCLC and the acquisition of the KRAS mutation to surpass EGFR inhibition. However, the combinational and interchanging usage of chemotherapy and TKI resulted in persistent and effective disease control.

Concurrent Radiotherapy with Erlotinib Followed by Maintenance Erlotinib in Patients with EGFR Mutation- Positive Adenocarcinoma Lung

To assess the efficacy and tolerability of erlotinib in combination with radiation therapy followed by maintenance therapy in Stage III and IV, epidermal growth factor receptor mutationpositive adenocarcinoma lung patients.The single-arm, quasi-experimental study was conducted at the Mayo Hospital, Lahore, Pakistan, from September 2013 to December 2014, and comprised patients with lung adenocarcinoma who were followed up till December 2017. The patients received concurrent radiation therapy (60- 70 Gy in 30-35 fractions) along with erlotinib 150mg/day, followed by erlotinib 150mg/day as maintenance therapy till disease progression. Primary endpoint was overall response rate according to Response Evaluation Criteria in Solid Tumours guideline version 1.0, while secondary endpoint was progression-free survival, overall survival and toxicity assessment with Common Terminology Criteria for Adverse Eventsversion 3.0. Before starting erlotinib, all patients received four cycles of standard chemotherapy with platinum doublets (Pemetrexed, Docetaxel, Paclitaxel, Gemcitabine). Data was analysed using SPSS 16..of the 62 patients initially enrolled, 49(79%) completed the study. Of them, 37(75.5%) patients were smokers. Mean age of the patients was 57.0±8.51 years (range: 31-73 years) and 40 (81.6%) were male subjects. Objective response rate was 71.4% (n=35). Median progression-free survival for stage III disease was 7.4 months and for stage IV disease 2.8 months. Corresponding median overall survival rates were 12.9 months and 5.5 months. Common adverse events observed were rash n=30(61.2%), fatigue n=21(42.9%) and diarrhoea n=18(36.7%).Concurrent radiotherapy with erlotinib was effective and well-tolerated in patients with locally advanced adenocarcinoma lung harbouring epidermal growth factor receptor mutation.

Quality of life analysis of Pemetrexed versus Erlotinib maintenance in EGFR mutation negative advanced non small cell lung cancer.

9024Background: Both Pemetrexed and Erlotinib have shown survival benefit when used as maintenance therapy in advanced non small cell lung cancer (NSCLC) after platinum doublet chemotherapy. Hence ...

432P - QTWiST analysis to compare the benefit of maintenance Erlotinib versus pemetrexed patients with EGFR non mutated NSCLC

Background: In an open label, Phase 3 randomised study, Pemetrexed maintenance after induction with 4-6 cycles of pemetrexed -Platinum therapy failed to prove its superiority over Erlotinib in patients with EGFR non mutated NSCLC. In this analysis we have assessed the benefit of erlotinib over Pemetrexed using quality adjusted time without symptom or toxicity analysis method. Methods: The overall survival in each arm was partitioned into 3 health states. TOX state (Time spent in grade 3 or above toxicity after randomization and before progression), TWiST state (Time spent after randomization before progression without grade 3 or above toxicity) and REL state (Time spent after progression). The mean QTWiST was calculated for each arm using utility coefficients of 0.65 for TOX, 0.71 for TWiST and 0.67 for REL states respectively. The difference in QTWiST and the 95% CI of difference were calculated using a nonparametric bootstrap. A p value of 0.05 was considered as significant. Results: The mean TOX duration was 2.216 days in Erlotinib arm versus 1.359 days in pemetrexed arm, p = 0.572. The mean TWiST duration was 215.85days in Erlotinib arm versus 217.605 days in pemetrexed arm, p = 0.945. The mean REL state duration was 198.620 days in Erlotinib arm versus 196.254 days in maintenance pemetrexed arm, p = 0.932. There was no statistically significant difference between the two arms in mean TOX duration, mean TWiST duration and mean REL state duration. The mean QTWiST was 287.770 days in Erlotinib arm versus 286.873 days in Pemetrexed arm. The difference was of -0.897 days (95% CI -22.475 - 20.681, p value 0.935). Conclusions: The mean QTWiST of Erlotinib arm was similar to maintenance Pemetrexed arm. Our results failed to prove the benefit of Erlotinib over Pemetrexed maintenance post induction with 4-6 cycles of pemetrexed -Platinum therapy in terms of quality adjusted time without toxicity. Legal entity responsible for the study: Department Of Medical Oncology Tata Memorial Hospital, Mumbai Funding: None Disclosure: All authors have declared no conflicts of interest.

SC23.04 Cooperative Groups in China: The CSCO Experience

SC23.04 Cooperative Groups in China: The CSCO Experience

Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study)

ObjectiveThe phase III IUNO trial assessed the benefit of maintenance erlotinib versus erlotinib at progression in advanced/metastatic non-small-cell lung cancer (NSCLC) that had not progressed following four cycles of platinum-based chemotherapy. Materials and MethodsPatients had stage IIIB/IV NSCLC, no known epidermal growth factor receptor (EGFR)-activating mutation, and objective response or disease stabilization after platinum-based induction chemotherapy. Central EGFR-mutation testing was undertaken on tumors from patients with unknown or wild-type EGFR status following local testing. Patients were randomized to receive blinded maintenance erlotinib 150mg/day (‘early erlotinib’) or placebo. Those who progressed on placebo received open-label erlotinib (‘late erlotinib’); patients who progressed on erlotinib received approved second-line chemotherapy or best supportive care. Primary endpoint: overall survival (OS). Results643 patients were randomized to receive maintenance erlotinib (n=322) or placebo (n=321). As of March 23, 2015, 242 (75.2%) OS events had occurred with ‘early erlotinib’ versus 235 (73.2%) with ‘late erlotinib’. Median OS was 9.7 and 9.5 months with ‘early erlotinib’ and ‘late erlotinib’, respectively (HR, 1.02, 95% CI: 0.85–1.22; log-rank p=0.82). No progression-free survival, objective response rate, or disease control rate benefit was observed with maintenance erlotinib. 410 patients entered the second-line phase of the study: 160 patients (50%) from the maintenance erlotinib arm and 250 patients (78%) from the maintenance placebo arm. The pattern of adverse events (AEs) was consistent with previous trials; 11 patients who received blinded erlotinib and 3 who received placebo died during the blinded maintenance phase due to nontreatment-related AEs. ConclusionsOS with maintenance erlotinib was not superior to second-line treatment in patients whose tumor did not harbor an EGFR-activating mutation. Safety results were consistent with the established safety profile of erlotinib. Thus, maintenance treatment with erlotinib in patients with advanced/metastatic NSCLC without EGFR-activating mutations is considered unfavorable.

Intercalated chemotherapy and erlotinib for non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations

ABSTRACTAmong attempts to delay development of resistance to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) with activating mutations of epidermal growth factor receptor (EGFR), intercalated therapy has not been properly evaluated. In a phase II trial, 38 patients with EGFR mutated NSCLC in advanced stage were treated with 4 to 6 3-weekly cycles of intercalated schedule with gemcitabine (1250 mg/m2, days 1 and 4), cisplatin (75 mg/m2, day 2) and erlotinib (150 mg, days 5 – 15), followed by continuous erlotinib as maintenance. In addition to standard radiologic evaluation according to RECIST, PET/CT was done prior to treatment and at 6 months, using PERCIST as a method for assessment of response. The primary endpoint was progression-free survival (PFS). In general, tolerance to treatment was good, even among 8 patients with performance status 2–3 and 13 patients with brain metastases; grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. Complete response (CR) or partial response (PR) were seen in 15 (39.5%) and 17 (44.7%) cases, respectively. All cases of CR were confirmed also by PET/CT. Median PFS was 23.4 months and median overall survival (OS) was 38.3 months. After a median follow-up of 35 months, 8 patients are still in CR and on maintenance erlotinib. In conclusion, intercalated treatment for treatment-naive patients with EGFR activating mutations leads to excellent response rate and prolonged PFS and survival. Comparison of the intercalated schedule to monotherapy with TKIs in a randomized trial is warranted.

Erlotinib added to bevacizumab as maintenance therapy and health-related quality of life in patients with metastatic colorectal cancer: Results of the GERCOR DREAM phase III trial.

3553Background: The DREAM phase III clinical trial aimed to assess the efficacy and tolerability of maintenance bevacizumab (B) plus erlotinib (E) after a bevacizumab-based induction therapy in pat...

Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer

ObjectivesThe FASTACT-2 study of intercalated erlotinib with chemotherapy in Asian patients found that EGFR mutations were the main driver behind the significant progression-free survival (PFS) benefit noted in the overall population. Further exploratory biomarker analyses were conducted to provide additional insight. Materials and methodsThis multicenter, randomized, placebo-controlled, double-blind, phase III study investigated intercalated first-line erlotinib or placebo with gemcitabine/platinum, followed by maintenance erlotinib or placebo, for patients with stage IIIB/IV non-small cell lung cancer (NSCLC). Provision of samples for biomarker analysis was encouraged but not mandatory. The following biomarkers were analyzed (in order of priority): EGFR mutation by cobas® test, KRAS mutation by cobas®KRAS test, HER2 by immunohistochemistry (IHC), HER3 by IHC, ERCC1 by IHC, EGFR gene copy number by fluorescence in-situ hybridization (FISH) and EGFR by IHC. All subgroups were assessed for PFS (primary endpoint), overall survival (OS), non-progression rate and objective response rate. ResultsOverall, 256 patients provided samples for analysis. Considerable overlap was noted among biomarkers, except for EGFR and KRAS mutations, which are mutually exclusive. Other than EGFR mutations (p<0.0001), no other biomarkers were significantly predictive of outcomes in a treatment-by-biomarker interaction test, although ERCC1 IHC-positive status was predictive of improved OS for the erlotinib arm versus placebo in EGFR wild-type patients (median 18.4 vs 9.5 months; hazard ratio [HR] HR=0.32, 95% confidence intervals [CI]: 0.14–0.69, p=0.0024). ConclusionActivating EGFR mutations were predictive for improved treatment outcomes with a first-line intercalated regimen of chemotherapy and erlotinib in NSCLC. ERCC1 status may have some predictive value in EGFR wild-type disease, but requires further investigation.

3071 A phase II study of carboplatin (Cb), pemetrexed (PEM), and bevacizumab (Bev) followed by Bev and erlotinib (Erl) maintenance for non-squamous non-small cell lung cancer (NS-NSCLC) with wild-type (WT) EGFR

3071 A phase II study of carboplatin (Cb), pemetrexed (PEM), and bevacizumab (Bev) followed by Bev and erlotinib (Erl) maintenance for non-squamous non-small cell lung cancer (NS-NSCLC) with wild-type (WT) EGFR

Intercalated chemotherapy and erlotinib for advanced NSCLC: high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutations.

BackgroundPharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC).Patients and methods.Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance.ResultsFifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2–3 (11 patients - 21%) and brain metastases (15 patients -28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months.ConclusionsWhile patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.

Phase 1/2 Clinical Trial of Re-irradiation With Pemetrexed and Erlotinib Followed by Maintenance Erlotinib for Recurrent and Second Primary Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Phase 1/2 Clinical Trial of Re-irradiation With Pemetrexed and Erlotinib Followed by Maintenance Erlotinib for Recurrent and Second Primary Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Randomized Trial of Erlotinib Plus Whole-Brain Radiotherapy for NSCLC Patients With Multiple Brain Metastases

BackgroundMedian survival of non-small cell lung cancer (NSCLC) patients with brain metastases is poor. We examined concurrent erlotinib and whole brain radiotherapy (WBRT) followed by maintenance erlotinib in patients with untreated brain metastases, given the potential radiosensitizing properties of erlotinib and its direct effect on brain metastases and systemic activity.MethodsEighty NSCLC patients with KPS of 70 and greater and multiple brain metastases were randomly assigned to placebo (n = 40) or erlotinib (100mg, n = 40) given concurrently with WBRT (20 Gy in 5 fractions). Following WBRT, patients continued with placebo or erlotinib (150mg) until disease progression. The primary end point was neurological progression-free survival (nPFS); hazard ratios (HRs) were calculated using Cox regression. All P values were two-sided.ResultsFifteen patients (37.5%) from each arm were alive and without neurological progression 2 months after WBRT. Median nPFS was 1.6 months in both arms; nPFS HR 0.95 (95% CI = 0.59 to1.54; P = .84). Median overall survival (OS) was 2.9 and 3.4 months in the placebo and erlotinib arms; HR 0.95 (95% CI = 0.58 to 1.55; P = .83). The frequency of epidermal growth factor receptor (EGFR) mutations was low with only 1 of 35 (2.9%) patients with available samples had activating EGFR-mutations. Grade 3/4 adverse event rates were similar between the two groups (70.0% in each arm), except for rash 20.0% (erlotinib) vs 5.0% (placebo), and fatigue 17.5% vs 35.0%. No statistically significant quality of life differences were found.ConclusionsOur study showed no advantage in nPFS or OS for concurrent erlotinib and WBRT followed by maintenance erlotinib in patients with predominantly EGFR wild-type NSCLC and multiple brain metastases compared to placebo. Future studies should focus on the role of erlotinib with or without WBRT in patients with EGFR mutations.

Epidermal growth factor receptor: will it ever become a therapeutic target in ovarian cancer?

Targeted therapies are increasingly being explored in the treatment of ovarian cancer. The epidermal growth factor receptor (EGFR) has received much attention as this pathway is overexpressed and/or amplified in ovarian cancer. Anti-EGFR tyrosine kinase inhibitors (TKIs) and monoclonal antibodies have been studied in combination with chemotherapy and as single agents in both the first-line and relapsed settings but unfortunately, the results have been disappointing. In this editorial, we review a recently published large randomized phase III trial conducted by Vergote et al. evaluating maintenance erlotinib in patients with ovarian, peritoneal, or fallopian tube cancer who experienced a response or stable disease (SD) after primary therapy. This study did not show a benefit to maintenance erlotinib and moreover, was not able to identify any subgroups that benefited from erlotinib. Testing for EGFR overexpression and/or amplification by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively, and mutation testing were performed on archival tumor tissue. Patients who were EGFR positive did have a worse progression-free survival (PFS) and overall survival (OS) but EGFR positivity or the presence of a mutation was not predictive of erlotinib efficacy. At this time, EGFR inhibition in ovarian cancer has not been successful and further targeting of this pathway requires an understanding of resistance mechanisms and the role of other pathways that interplay with EGFR.