A Comparative Study Evaluating the Quality of Life and Survival Outcomes in Patients Receiving Chemotherapy Versus Oral Tyrosine Kinase Inhibitor in the Third Line and Beyond Setting for Advanced NSCLC.

Introduction: The outcomes in advanced NSCLC have improved owing to the availability of more effective systemic and improved supportive care. This has increased the number of patients who seek treatment in the third line and beyond setting. We conducted this study to compare the quality of life (QoL), toxicity, and outcomes in patients receiving chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) in this setting. Methods: In this phase 3, randomized, open-label study, patients with stage III or IV NSCLC with disease progression on at least two prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior EGFR TKI exposure, and stable brain metastases (if any) were included. Patients were randomized to receive chemotherapy (gemcitabine or docetaxel or paclitaxel or vinorelbine) or an EGFR TKI (erlotinib or gefitinib). The primary end point was the change in QoL at 8 to 10 weeks; the secondary outcomes were safety and overall survival (OS). Patients underwent clinical evaluation at every visit, and toxicity was assessed as per Common Terminology Criteria for Adverse Events version 4.03. A radiological tumor response assessment was done every 8 to 12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C30 and LC13 questionnaires. The change in QoL scores was calculated as the difference between scores at baseline and scores at 8 to 10 weeks (Δ) for each QoL domain. The Mann-Whitney U test was used to compare the mean difference (Δ) for each domain. OS and progression-free survival (PFS) were determined using the Kaplan-Meier method and Cox proportional regression analysis. Results: A total of 246 patients were enrolled in the study, with 123 in each arm. There was a male predominance with 69.1% male patients in the chemotherapy arm and 70.7% in the EGFR TKI arm. The median age of patients in the chemotherapy arm was 54 years and 55 years in the chemotherapy and EGFR TKI arms, respectively. There was no significant difference in the change in QoL at baseline and the second visit (Δ) in both arms in all domains of EORTC QLQ C30 except cognitive function (p = 0.0045) and LC13 except alopecia (0.01249). The mean Δ Global Health Status was -28 in the chemotherapy arm and -26.8 in the EGFR TKI arm; this was not statistically significant (p = 0.973). The median follow-up was 88.1 months (95% confidence interval [CI]: 39.04-137.15). On the intention-to-treat analysis, the median PFS was 3.13 months (95% CI: 2.15-4.11) in the chemotherapy arm and 2.26 months (95% CI: 2.1-2.43) in the EGFR TKI arm, with hazard ratio at 1.074 (95% CI: 0.83-1.38) (p = 0.58). There were 120 deaths in each arm. The median OS was 7.63 months (95% CI: 5.96-9.30) in the chemotherapy arm and 7.5 months in the EGFR TKI arm (95% CI: 5.85-9.14); hazard ratio at 1.033 (95% CI: 0.80-1.33) (p = 0.805). The toxicity profile was similar in both arms except for a significantly higher incidence of fatigue (p = 0.043), peripheral neuropathy (0.000), alopecia, hypokalemia (0.037), and pedal edema (0.007) in the chemotherapy arm and dry skin (p = 0.000) and skin rash (p = 0.019) in the EGFR TKI arm. Conclusions: There was no significant difference in most QoL scales (except cognitive function and alopecia), OS, and PFS of patients with advanced NSCLC receiving an EGFR TKI as compared with chemotherapy TKI in the third-line setting. The toxicity profile is consistent with the known toxicities of the agents.

Clinical Utility of Liquid Biopsy (Cell-free DNA) Based EGFR Mutation Detection Post treatment Initiation as a Disease Monitoring Tool in Patients With Advanced EGFR-mutant NSCLC.

INTRODUCTION: Plasma cfDNA-based mutation analysis has shown disease-monitoring potential in various cancers. We assessed the potential of cfDNA-based EGFR mutation testing as a monitoring tool in patients with NSCLC. PATIENTS AND METHODS: Patients with NSCLC harboring EGFR mutations receiving first-line treatment as per institutional protocol were enrolled. EGFR mutation status was determined using plasma samples at baseline and post treatment initiation. Patients in whom EGFR mutation was detected or persisted after treatment initiation were considered circulating tumor DNA (ctDNA)-positive. Progression-free survival (PFS) and overall survival (OS) for ctDNA-positive and negative patients post treatment initiation were the primary endpoints; concordance for baseline EGFR status between tissue and plasma and proportion of patients who were ctDNA-positive post treatment initiation were the secondary endpoints. RESULTS: We enrolled 158 patients; 76 received gefitinib, and 82 received gefitinib plus chemotherapy. Median follow-up duration was 42 months. About 25% of patients were ctDNA-positive post treatment initiation. Median PFS for ctDNA-negative patients post treatment initiation was 14 (95% confidence interval [CI], 12.0-17.0) months, while that for ctDNA-positive patients was 8 (95% CI, 6.0-10.0) months. Median OS for ctDNA-negative patients post treatment initiation was 27 (95% CI, 24.0-32.0) months, while that for ctDNA-positive patients was 15 (95% CI, 11.0-19.0) months. Concordance at baseline between tissue and plasma samples was 75.4%. CONCLUSION: Plasma-based EGFR mutation detection post treatment initiation can be used as a predictive marker for outcome in patients with EGFR-mutant NSCLC receiving first-line treatment.

Audit of screen failure in 15 randomised studies from a low and middle-income country.

Background: Growth and development in patient management occurs via randomised studies. Screen failure is a significant hurdle while conducting randomised studies. There is limited data available from low and middle-income countries about factors resulting in screen failure. Hence, this audit was performed to identify the proportion of patients who screen failed and to elucidate reasons for the same. Methods: This was an audit of 15 randomised studies performed by medical oncology solid tumour unit II of Tata Memorial Centre. The screening logs of these studies were acquired. From the screening logs, data regarding the number of patients who had screen failed & reason for the same were obtained. Descriptive statistics were performed. Results: A total of 7,481 patients were screened for 15 randomised clinical studies. Out of these, 3,666 (49.0%) patients were enrolled into trials and 3,815 (51.0%) screen failed. The most common reason for screen failure was 'not meeting inclusion criteria' (54.9%) followed by declining to take treatment (22.2%). Other factors that affect enrolment were 'not willing to stay in the locality of the trial site' (6.2%), being recruited in other studies (3.7%), poor performance status (PS) (3.4%), non-compliance (2.2%), meeting exclusion criteria (0.9%) and 'other' (6.5%). Conclusion: The commonest causes of screen failure in lower and middle-income countries are non-meeting of inclusion criteria followed by declining to take treatment, not willing to stay in locality of trial site, recruited into other studies, poor PS, non-compliance, meeting exclusion criteria & 'other'. This information would help analysing and hence planning of newer strategies to decrease the rate of screen failure.

An observational study to evaluate factors predicting survival in patients of non-small cell lung cancer with poor performance status in resource-constrained settings.

BACKGROUND: A significant proportion of non-small cell lung cancer (NSCLC) patients present with poor performance status (PS) at baseline are almost always excluded from the clinical trials leading to availability of only limited data in this subgroup. PATIENTS AND METHODS: This was an observational single institutional study. The eligibility criteria for inclusion were a histologic or cytologic diagnosis of advanced NSCLC and Eastern Cooperative Oncology Group PS 3 or 4. All patients coming between June 2015 and December 2018 were evaluated for inclusion in this study. RESULTS: A total of 245 patients were enrolled in the study. The median age of the patients was 63 years (range 25-89), 142 (58%) were male, 196 (80%) had adenocarcinoma histology and 192 (78.4%) has PS 3 while rest (21.6%) had PS 4. Out of 245 patients, 192 (78.4%) received oral tyrosine kinase inhibitors (TKI) and supportive care, 45 (18.4%) received supportive care alone, while 8 (3.2%) patients received chemotherapy along with supportive care. Median overall survival (OS) was 3 months (95% CI: 1.8-4.2) in patients who received oral TKI versus 1 month (1.0-2.9) in patients who received supportive care alone (log-rank p = 0.013). The median OS for epidermal growth factor receptor (EGFR) mutant patients who received oral TKI was 12 months (95% CI: 7.7-16.3), while it was 3 months (95% CI: 1.5-4.5) for patients who were EGFR wild-type and received TKI on compassionate basis (HR = 0.50; 95% CI: 0.32-0.77; p = 0.001). CONCLUSIONS: The use of oral TKI on a compassionate basis led to improvement in survival in the overall cohort of the patients; this was principally driven by EGFR-mutated patients.

Reasons for Initiation of Areca Nut and Related Products in Patients with Oral Submucous Fibrosis within an Endemic Area in Gujarat, India.

Background: While the patterns of consumption of areca nut and its by-products (ANBP) vary across South Asia and the rest of the world, all users share the probable severe outcome of oral submucous fibrosis (OSMF), and this is well reported. The role of psychosocial drivers of habit initiation and addiction is reported less. Objective: To reveal the burden of ANBP abuse, exploring the psychosocial relationship between sex, age at first exposure (AFE), the reason for initiation (RFI) with the type of habit (TOH). Methodology: Data came from the prospective hospital-based study conducted at K.M. Shah Dental College and Hospital covering years 2017 and 2018. Patients with oral lesions were assessed with complete history recording demographics, TOH, AFE, RFI, duration of habit, and clinical diagnosis of any oral and systemic diseases. Patients with a history of scleroderma, facial burns, and oral malignancy were excluded. Results: Of the 13,874 patients, 9.89% reported ANBP. We included 1000 OSMF patients. The mean age of the study cohort was 38.97 ± 14.29 years, with a range of 17-75 years. Males constituted the majority (80.1%). The most common TOH reported was regular use of gutkha (60.1%) followed by mawa (31.4%) with tension and stress (30.3%) being the most common RFI among the cohort. TOH was notably different in relation to AFE. Interestingly, mawa chewing (38.69%) was observed more in females. Importance: This study reveals the burden of ANBP abuse and reports the complex psychosocial relationships between sex, AFE, and RFI with TOH in OSMF patients in this high incidence population.

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer.

PURPOSE: Standard first-line therapy for EGFR-mutant advanced non-small-cell lung cancer (NSCLC) is an epidermal growth factor receptor (EGFR)-directed oral tyrosine kinase inhibitor. Adding pemetrexed and carboplatin chemotherapy to an oral tyrosine kinase inhibitor may improve outcomes. PATIENTS AND METHODS: This was a phase III randomized trial in patients with advanced NSCLC harboring an EGFR-sensitizing mutation and a performance status of 0 to 2 who were planned to receive first-line palliative therapy. Random assignment was 1:1 to gefitinib 250 mg orally per day (Gef) or gefitinib 250 mg orally per day plus pemetrexed 500 mg/m2 and carboplatin area under curve 5 intravenously every 3 weeks for four cycles, followed by maintenance pemetrexed (gefitinib plus chemotherapy [Gef+C]). The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), response rate, and toxicity. RESULTS: Between 2016 and 2018, 350 patients were randomly assigned to Gef (n = 176) and Gef+C (n = 174). Twenty-one percent of patients had a performance status of 2, and 18% of patients had brain metastases. Median follow-up time was 17 months (range, 7 to 30 months). Radiologic response rates were 75% and 63% in the Gef+C and Gef arms, respectively (P = .01). Estimated median PFS was significantly longer with Gef+C than Gef (16 months [95% CI, 13.5 to 18.5 months] v 8 months [95% CI, 7.0 to 9.0 months], respectively; hazard ratio for disease progression or death, 0.51 [95% CI, 0.39 to 0.66]; P < .001). Estimated median OS was significantly longer with Gef+C than Gef (not reached v 17 months [95% CI, 13.5 to 20.5 months]; hazard ratio for death, 0.45 [95% CI, 0.31 to 0.65]; P < .001). Clinically relevant grade 3 or greater toxicities occurred in 51% and 25% of patients in the Gef+C and Gef arms, respectively (P < .001). CONCLUSION: Adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC.

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.

Phase III Non-inferiority Study Evaluating Efficacy and Safety of Low Dose Gemcitabine Compared to Standard Dose Gemcitabine With Platinum in Advanced Squamous Lung Cancer.

BACKGROUND: Prolonged infusion of low dose gemcitabine (PLDG) in combination with platinum has shown promising activity in terms of improved response rate and progression free survival (PFS); especially in squamous non-small cell lung cancer (NSCLC). Hence, we conducted a phase 3 randomized non-inferiority study with the primary objective of comparing the overall survival (OS) between PLDG and standard dose of gemcitabine with platinum. METHODOLOGY: Adult subjects (age ≥ 18 years), with stages IIIB-IV, NSCLC (squamous) and ECOG performance status of ≤ 2 were randomized 1:1 into either carboplatin with standard dose gemcitabine (1000 mg/m2 intravenous over 30 min, days 1 and 8) (STD-G arm) or carboplatin along with low dose gemcitabine (250 mg/m2 intravenous over 6 h, days 1 and 8) (LOW-G arm) for a maximum of 6 cycles. Tumor response was assessed by RECIST criteria version 1.1 every 2 cycles till 6th cycle and thereafter at 2 monthly intervals till progression. The primary endpoint was overall survival. 308 patients were randomized, 155 in STD-G arm and 153 in LOW-G arm, respectively. RESULTS: The median overall survival in STD-G arm was 6.8 months (95%CI 5.3-8.5) versus 8.4 months (95%CI 7-10.3) in the LOW-G arm (HR-0.890 (90%CI 0.725-1.092). The results with per protocol analysis were in line with these results. There was no statistical difference in progression free survival (HR-0.949; 90%CI 0.867-1.280) and adverse event rate between the 2 arms. CONCLUSION: This study suggests that PLDG is an alternative to the standard gemcitabine schedule in squamous NSCLC, and either of these can be selected subject to patient convenience.

Thromboembolic events in patients with advanced stage non-small cell lung cancer treated with platinum-based chemotherapy: a prospective observational study.

OBJECTIVES: Cancer is frequently complicated by thromboembolic events (TEs). We aimed to determine the incidence of TEs in lung cancer patients treated with platinum-based chemotherapy and study patients' baseline and treatment attributes correlating with its onset. MATERIALS AND METHODS: Advanced lung cancer patients started on platinum-based chemotherapy were evaluated at baseline and during routine visits for the development of TEs. The duration of follow-up was 4 weeks from the last chemotherapy. A TE occurring between the first dose of chemotherapy and 4 weeks after the last dose was considered to be chemotherapy associated. RESULTS: Of the 165 patients on platinum chemotherapy who completed follow-up, TEs occurred in 4.8% (8 out of 165) patients. Among these, three patients had developed venous pulmonary thromboembolism and five patients had developed cerebral infarction, out of which four had arterial cerebral infarction and one patient had a superior sagittal sinus thrombosis. The majority of events (7 out of 8) occurred within 100 days of starting platinum chemotherapy. Overall, the median time until occurrence of TE was 48 days (range, 10-130 days). None of the presumed risk factors were found be associated with the occurrence of TEs on univariate analysis. CONCLUSIONS: Advanced lung cancer patients on platinum chemotherapy are predisposed to thromboembolism due to many factors. Despite its lower incidence in our study, exclusion of patients with prior thrombosis suggests the incidence of de novo thrombosis, and hence raises a valid question of the need of thromboprophylaxis in a selected group of patients.

Efficacy of gefitinib in epidermal growth factor receptor-activating mutation-positive nonsmall cell lung cancer: Does exon 19 deletion differ from exon 21 mutation?

BACKGROUND: This study was designed to evaluate the differential effect of epidermal growth factor receptor (EGFR) mutation status (exon 19 vs. 21) on progression-free survival (PFS) and overall survival (OS) in treatment-naïve advanced EGFR mutation-positive nonsmall cell lung cancer (NSCLC) treated with gefitinib as first-line agent. METHODS: This was a post hoc analysis of EGFR-mutated (exon 19 and 21) advanced-stage (Stage IIIB or IV), chemotherapy-naive NSCLC patients treated with gefitinib as first line in a phase 3 randomized study. Patients were treated with gefitinib 250 mg daily. Patients underwent axial imaging for response assessment on D42, D84, D126, and subsequently every 2 months till progression. Responding or stable patients were treated until progression or unacceptable toxicity. SPSS was used for statistical analysis. Kaplan-Meier method was used for survival estimation and log-rank test for comparison. Cox proportion hazard model was used for multivariate analysis. RESULTS: One hundred and forty-one patients were eligible for analysis, of which 78 were males and 63 were females. A total of 127 patients (90.1%) were ECOG 0-1 while 14 patients (9.1%) were ECOG >1. Exon 21 mutation was present in 65 patients (46.1%) and exon 19 mutation in 76 patients (53.9%). One hundred and thirty-three of 141 patients were evaluable for response. Response rate of patients having exon 19 mutation was 72.9% (51 patients, n = 70) while it was 55.6% in patients having exon 21 mutation (35 patients, n = 63) (P = 0.046). Median PFS in exon 19-mutated patients was 9.3 months (95% confidence interval [CI] 6.832-11.768) compared to 7.8 months (95% CI 5.543-10.0) (P = 0.699) in exon 21-mutated patients. The median OS in exon 19-mutated patients was 19.8 months (95% CI 16.8-22.7), and it was 16.5 months (95% CI 10.9-22.1) in exon 21-mutated patients (P = 0.215). CONCLUSION: There were no differential outcomes in the Indian patients of advanced-stage NSCLC with exon 19 and 21 EGFR mutations treated with gefitinib.

Phase III randomized trial comparing intravenous to oral iron in patients with cancer-related iron deficiency anemia not on erythropoiesis stimulating agents.

AIM: We aimed to find the optimal route of iron supplementation in patients with malignancy and iron deficiency (true or functional) anemia not receiving erythropoiesis stimulating agents (ESA). METHODS: Adult patients with malignancy requiring chemotherapy, hemoglobin (Hb) <12 g/dL and serum ferritin <100 mcg/mL, transferrin saturation <20% or hypochromic red blood cells >10% were randomized to intravenous (IV) iron sucrose or oral ferrous sulfate. The primary endpoint was change in Hb from baseline to 6 weeks. Secondary endpoints included blood transfusion, quality of life (QoL), toxicity, response and overall survival. RESULTS: A total of 192 patients were enrolled over 5 years: 98 on IV arm and 94 on oral arm. Median age was 51 years; over 95% patients had solid tumors. The mean absolute increase in Hb at 6 weeks was 0.11 g/dL (standard deviation [SD]: 1.48) in IV arm and -0.16 g/dL (SD: 1.36) in oral arm, P = 0.23. Twenty-three percent patients on IV iron and 18% patients on oral iron had a rise in Hb of ≥1 g/dL at 6 weeks, P = 0.45. Thirteen patients (13.3%) on the IV iron arm and 14 patients (14.9%) on the oral arm required blood transfusion, P = 1.0. Gastrointestinal toxicity (any grade) developed in 41% patients on IV iron and 44% patients on oral iron, P = 1.0. 5 patients on IV iron and none on oral iron had hypersensitivity, P = 0.06. QoL was not significantly different between the two arms. CONCLUSION: IV iron was not superior to oral iron in patients with malignancy on chemotherapy and iron deficiency anemia.

Efficacy of Second-Line Pemetrexed-Carboplatin in EGFR-Activating Mutation-Positive NSCLC: Does Exon 19 Deletion Differ from Exon 21 Mutation?

BACKGROUND: It is unknown whether the outcomes of second-line pemetrexed-carboplatin chemotherapy administered after progression on gefitinib are dependent on type of EGFR mutation present at baseline. METHOD: Adult non-small-cell lung cancer patients, with exon 19 deletion or exon 21 L858R mutation, who progressed on gefitinib and received pemetrexed-carboplatin chemotherapy were selected for this analysis. RESULT: 55 patients received pemetrexed-carboplatin as second-line treatment. Response rates in evaluable patients were 39.3% in exon 19 patients (n = 28) and 33.3% in exon 21 patients (n = 15) (p = 0.752, Fisher's exact 2-sided p value). The median PFS in exon 19 and 21 cohorts was 5.900 months (95% CI: 4.274-7.526) and 4.767 months (95% CI: 1.374-8.159), respectively. The median overall survival in exon 19 patients was (11.8 months, 95% CI: 9.916-13.684 months) significantly better than that seen in exon 21 mutation patients (6.2 months, 95% CI: 4.215-8.118 months, p = 0.024) on univariate analysis; however, on multivariate analysis, this association was not confirmed (HR = 0.361, 95% CI: 0.090-1.439, p = 0.149). CONCLUSION: Exon 19 deletion has no impact on PFS and OS in EGFR-mutated patients treated with second-line pemetrexed-carboplatin.

Impact of exon 19 versus exon 21 EGFR-activating mutation on outcomes with upfront pemetrexed-carboplatin chemotherapy.

BACKGROUND: EGFR mutation subtype is a recognised factor impacting outcomes of patients receiving oral tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Evidence for the effect of this factor on outcomes in patients receiving pemetrexed is limited. METHODS: We completed a study comparing pemetrexed-platinum combination versus oral TKI in EGFR mutation-positive patients in lung cancer. We analysed the impact of EGFR mutation subtype, specifically, exon 19 and 21 on the PFS and OS of patients treated with pemetrexed (500 mg/m2 on day 1) and carboplatin (AUC 5 on day 1) as first-line therapy. Patients underwent axial imaging for response assessment on D42, D84, D126 and subsequently every two months till progression. Patients post-progression were treated with gefitinib. RESULTS: Fifty-one patients (36%) had exon 21 mutation, while 92 patients (64%) had exon 19 mutation. Response rates in evaluable patients was 47.7% in exon 19 patients (41 patients, n = 86) and 42.9 % in exon 21 patients (18 patients, n = 42). There was a significant increase in median overall survival for patients with exon 19 mutations (24.5 months, 95% CI: 21.3-27.7 months ) over the exon 21-mutated patients (18.1 months, 95% Cl: 13.5-22.6 months, p = 0.002). This differential impact was due to second-line gefitinib having a differential outcome on these mutations. CONCLUSION: Pemetrexed-based chemotherapy does not have a differential impact on exon 19- or exon 21-mutated patients. However, second-line treatment with gefitinib has a favourable response and outcome in exon 19-mutated patients.

Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma.

OBJECTIVE: Oral tyrosine kinase inhibitor has been shown to prolong progression-free survival (PFS) in estimated glomerular filtration rate (EGFR) mutation positive adenocarcinoma; however, the comparator arm has not included the current standard adenocarcinoma regimen (pemetrexed carboplatin induction followed by maintenance pemetrexed) and patients from Indian subcontinent. Hence, this study was carried out in Indian patients to compare gefitinib with the above-mentioned chemotherapy regimen. METHODS: This was an open-labelled, randomised, parallel group study comparing gefitinib (250 mg orally daily) with pemetrexed (500 mg/m2) and carboplatin (area under the curve 5) doublet intravenous induction chemotherapy regimen followed by maintenance pemetrexed (500 mg/m2) in patients with EGFR-activating mutation-positive stage IIIB or stage IV adenocarcinoma lung in the first-line setting. The primary endpoint for the study was PFS. 260 patients were required to demonstrate a 50% improvement in PFS of gefitinib over chemotherapy, with 80% power and 5% type 1 error. With an expected 5% dropout rate, the sample size was 290 patients. RESULTS: The median PFS in gefitinib arm was 8.4 months (95% CI 6.3 to 10.5 months) compared with 5.6 months (95% CI 4.2 to 7.0 months) in pemetrexed-carboplatin arm (HR: 95% CI 0.513 to 0.851; p -0.001). The impact of gefitinib on PFS was seen across all subgroups.There was no statistically significant difference in overall survival between the two arms. Haematologicalgrade3-4toxicities likeanaemia,neutropaenia and thrombocytopaenia were common in the pemetrexed-carboplatin arm while grade3-4 acneiform rash and diarrhoeawere common in the gefitinib arm. CONCLUSION: The study confirms the superiority of gefitinib in prolonging PFS against the most active chemotherapy regimen of pemetrexed-carboplatin followed by maintenance pemetrexed in EGFR-mutated lung adenocarcinoma. The median PFS in Indian patients in gefitinib arm is similar to that reported in east Asians and Caucasians.