Gefitinib Maintenance Research Articles

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.

Clinical study of gefitinib maintenance therapy after concurrent radiotherapy and chemotherapy for locally advanced NSCLC with EGFR sensitive mutations.

87 Background: To investigate the value of Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in the maintenance therapy of locally advanced NSCLC after concurrent radiotherapy and chemotherapy. Methods: From Jan 2010 to Jan 2015, 166 patients with locally advanced NSCLC were treated in JCH. Total 86 patients with no progress after concurrent radiotherapy and chemotherapy were selected. Within 2 to 6 weeks after therapy, eligible patients received TKI (Gefitinib 250mg/day) or were observed for 1 year. If disease progresses or intolerable adverse reactions occur, the treatment should be discontinued. Chest and abdomen CT exam were performed 2 weeks before TKI treatment, and every 2 months thereafter. The same assessment techniques were used throughout the study. Therapeutic evaluation refers to the RECIST. SPSS 19.0 was used for data analysis and processing. Survival analysis was performed by Kaplan-Meier method. Results: In TKI drug group, CR 6 cases, PR 18 cases, SD 12 cases, PD 7 cases; in observation group, CR 3 cases, PR 11 cases, SD 13 cases, PD 16 cases. The CR + PR were 54.5% and 31.8% respectively, P = 0.031. The CR + PR + SD were 81.8% and 61.4% respectively, P = 0.033. The objective remission rate and disease control rate of TKI group were higher than those of observation group. The TTP in TKI group was 13.6 months (CI: 12.88-14.32 months) and that in observation group was 10.8 months (CI: 9.87-11.73 months), P = 0.001. The median OS of TKI group was 34.5 months (CI: 32.12-36.88 months) and that of observation group was 30.3 months (CI: 28.64-31.96 months), P = 0.029. Conclusions: 1. The objective remission rate and disease control rate of TKI group were higher than those of placebo group. 2. Ohitinib was not on the market in China at the time of this study and economic reason, so palliative chemotherapy was the main way to treat condition, and no third-generation TKI drugs were used. This may be one of the reasons why the total OS in this study was not long. 3. TKI drugs can improve the disease control rate and prolong the survival time of patients with locally advanced NSCLC after concurrent radiotherapy and chemotherapy, and have less side effects.

ES02.02 Management of EGFR LA Disease

ES02.02 Management of EGFR LA Disease

Gefitinib for advanced non-small cell lung cancer.

Gefitinib for advanced non-small cell lung cancer.

Intercalating and maintenance gefitinib plus chemotherapy versus chemotherapy alone in selected advanced non-small cell lung cancer with unknown EGFR status

Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) are standard treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. However, EGFR mutation testing is not attainable in approximately 20% of patients. The current study examined intercalating and maintaining gefitinib treatment in stage IIIB/IV non-squamous NSCLC, never or former light smoking patients with unknown EGFR mutation status. Briefly, 219 patients who achieved stable disease (SD) with gemcitabine (1250 mg/m2) plus carboplatin (5 AUC) were randomized at 1:1 ratio to continue chemotherapy (n = 110) or intercalating gefitinib (250 mg/day on days 15–25 of each cycle until disease progress (n = 109). Progression-free survival (PFS) was 9.7 vs. 4.2 month in the gefitinib vs. control arm (HR: 0.41, 95% CI: 0.31–0.56; P < 0.001). Overall survival (OS) was also longer in the gefitinib arm (20.1 vs. 15.4 months; HR: 0.68; 95% CI 0.48–0.97; P = 0.0323). Adverse events, including diarrhea, dermal reaction and thrombocytopenia, were more common in the gefitinib arm. In conclusion, intercalating and maintenance gefitinib treatment is a viable option for advanced NSCLC patients with unknown EGFR mutation status in subpopulations with high EFGR mutation rate.

Palliative Radiotherapy with Concomitant and Maintenance Gefitinib for the Management of Locally Advanced Adenocarcinoma Lung Patients Unfit For Radical Treatment

Palliative Radiotherapy with Concomitant and Maintenance Gefitinib for the Management of Locally Advanced Adenocarcinoma Lung Patients Unfit For Radical Treatment

Study of gefitinib maintenance in unselected patients with metastatic primary lung adenocarcinoma: A descriptive study.

Maintenance treatment of patients with advanced nonsmall cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of this study was to investigate the efficacy, safety, and tolerability of the epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitor, i.e., gefitinib in the maintenance setting irrespective of EGFR status. Patients aged 18 years or older of Indian origin, who had a life expectancy of >12 weeks with histologically or cytologically confirmed Stage IV NSCLC, the WHO performance status of 0-2, and who had completed four to six cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects were included in the study. The primary endpoint of the study was progression-free survival in the intention-to-treat population. Twenty-five patients with a median age of 55 years (40-68) were included in the study. The median progression-free survival (PFS) for the entire group was 8 months (95% confidence interval [CI] =1.45-14.54) had not reached for EGFR-positive patient, but in the EGFR negative cohort, the PFS was 4.98 months (hazard ratio = 0.092, 95% CI = 3.4-6.5, P = 0.01). The median overall survival (OS) of the study group was 15 months (95% CI = 3.7-26.4), all patients with EGFR positive were alive (100% survival). The median OS for EGFR negative group was about 6.3 months. The major toxicity observed was rash/acne in 15 patients, pruritus in 7 patients, and one patient had Grade 4 pneumonitis. Gefitinib maintenance is safe, well-tolerated therapy, produces significant PFS and OS benefit in EGFR mutation-positive patient. It is definitely not a choice for EGFR negative group. In EGFR unknown group, the role of maintenance still needs to be explored.

MTE17.02 Maintenance Therapy versus Early Second-Line Therapy in Advanced NSCLC

MTE17.02 Maintenance Therapy versus Early Second-Line Therapy in Advanced NSCLC

PC02.02 Pro Chemotherapy

PC02.02 Pro Chemotherapy

Comparison of the efficacy and tolerability of gefitinib with pemetrexed maintenance after first-line platinum-based doublet chemotherapy in advanced lung adenocarcinoma: single-center experience.

PurposeBoth gefitinib and pemetrexed maintenance were effective therapies for advanced lung adenocarcinoma, but which is better is unclear. For patients with advanced lung adenocarcinoma, we have no idea whether we should choose gefitinib or pemetrexed maintenance in clinical practice. Here, we assessed the efficacy and tolerability of gefitinib versus pemetrexed maintenance in these patients.Patients and methodsA total of 101 patients were identified and divided into gefitinib (n=53) or pemetrexed (n=48) maintenance. Epidermal growth factor receptor (EGFR) status of tumors was analyzed in 67 patients. Disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between the two groups.ResultsThe results showed that DCR (79.2% vs 75%, P=0.642) was similar between gefitinib and pemetrexed groups. The PFS of gefitinib was significantly longer than that of pemetrexed (8 months vs 5.4 months, hazard ratio [HR]: 0.520, 95% confidence interval [CI]: 0.341–0.791, P=0.002); however, the OS was similar (19.9 months vs 18.8 months, HR: 1.006, 95% CI: 0.664–1.525, P=0.977). In EGFR mutation-positive patients, PFS was significantly longer in gefitinib (12 months vs 5.4 months; HR: 0.158, 95% CI: 0.074–0.333, P<0.001), whereas in EGFR wild-type subgroup gefitinib had a significantly shorter PFS than that by pemetrexed (2.5 months vs 5 months; HR: 2.822, 95% CI: 1.137–7.005, P=0.025). Cox multivariate regression analysis of PFS for overall population showed that smoking status (P=0.001) and maintenance regimens (P=0.013) were independent prognostic factors for PFS. Both gefitinib and pemetrexed were well tolerated.ConclusionGefitinib compared with pemetrexed as maintenance therapy had a significantly longer PFS and a similar OS with good tolerability in patients with advanced lung adenocarcinoma. Moreover, for EGFR mutation-positive patients, gefitinib maintenance had a significantly longer PFS; however, pemetrexed maintenance was considered more effective for EGFR wild-type patients.

Early clinical results of a phase II trial evaluating neoadjuvant chemotherapy followed by chemoradiation and maintenance gefitinib in locally advanced cervical cancer.

e17014Background: Neoadjuvant chemotherapy (NACT) followed by chemoradiation (CTRT) is hypothesized to improve survival in locally advanced cervical cancer (LACC) by reducing distant metastasis. Im...

Phase II study of carboplatin and pemetrexed followed by gefitinib for patients with advanced non-small cell lung cancer harboring sensitive EGFR mutation.

e20581Background: To evaluate the efficacy, safety and survival of carboplatin and pemetrexed (Cb/Pem) as induction therapy followed by gefitinib (Gef) maintenance in patients with EGFR-positive ad...

First-Line Pemetrexed plus Cisplatin followed by Gefitinib Maintenance Therapy versus Gefitinib Monotherapy in East Asian Never-Smoker Patients with Locally Advanced or Metastatic Nonsquamous Non–Small Cell Lung Cancer: Final Overall Survival Results from a Randomized Phase 3 Study

IntroductionThe primary analysis of this open-label, randomized, multicenter phase 3 study revealed no significant difference in progression-free survival between pemetrexed plus cisplatin followed by maintenance gefitinib (PC/G) and gefitinib monotherapy (G) in patients with advanced nonsquamous non–small cell lung cancer (NSCLC) and unknown epidermal growth factor receptor gene (EGFR) mutation status; however, the hazard ratio favored PC/G. This report describes the final overall survival (OS) results. MethodsChemonaive, East Asian light ex-smokers/never-smokers with advanced nonsquamous NSCLC and unknown EGFR mutation status were randomized (1:1) to PC/G (n = 118) or G (n = 118). EGFR mutation status was retrospectively determined for 76 patients, 52 (68.4%) of whom had EGFR-mutated tumors (exon 19 deletions in 26 and L858R point mutation in 24). OS was analyzed by the Kaplan-Meier method. The study was registered at ClinicalTrials.gov (NCT01017874). ResultsMedian OS was similar in the PC/G (26.9 months) and G (27.9 months) groups (hazard ratio = 0.94, 95% confidence interval: 0.68–1.31, p = 0.717). Median OS was longer with PC/G than with G in patients with EGFR wild-type tumors (28.4 versus 8.9 months) and longer with G than with PC/G in patients with EGFR-mutated tumors (45.7 versus 32.4 months), especially those with exon 19 deletions. Second-line postdiscontinuation therapy was common and included chemotherapy (PC/G, 41 of 118 [34.7%]; G, 73 of 118 [61.9%]) and rechallenge with an EGFR tyrosine kinase inhibitor (PC/G, 27 of 118 [22.9%]; G, 9 of 118 [7.6%]). ConclusionsThe progression-free survival and OS results from this study further demonstrate the importance of determining EGFR mutation status to select the most appropriate first-line treatment for patients with advanced NSCLC.

First-Line Pemetrexed Plus Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in East Asian Never-Smoker Patients With Locally Advanced or Metastatic Nonsquamous Non–Small-cell Lung Cancer: Quality of Life Results From a Randomized Phase III Trial

BackgroundThe efficacy results from an open-label, randomized, multicenter study found no significant difference in progression-free survival between pemetrexed plus cisplatin followed by maintenance gefitinib (PC/G) and gefitinib monotherapy (G) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) and unknown epidermal growth factor receptor (EGFR) mutation status (hazard ratio favored PC/G). The present report describes the quality of life (QoL) results from that trial. Patients and MethodsChemotherapy-naive, East Asian, light ex-smokers or never-smokers with advanced nonsquamous NSCLC and unknown EGFR mutation status (n = 236) were randomly assigned (1:1) to PC/G or G. EGFR mutation status was subsequently determined for 74 patients. The symptoms and QoL were assessed using the Lung Cancer Symptom Scale (LCSS). The time to worsening of symptoms (TWS) was analyzed using the Kaplan-Meier method. ResultsIn the overall population, the TWS was generally longer in the G group (n = 109) than in the PC/G group (n = 109) for the LCSS symptoms classified as treatment-related (loss of appetite, fatigue) and tumor-related (cough, dyspnea, hemoptysis, pain). In the subgroup of patients with wild-type EGFR, the TWS was generally longer in the PC/G group (n = 13) than in the G group (n = 8) for the tumor-related LCSS symptoms. ConclusionIn this study population clinically selected to respond to gefitinib, the LCSS scores were more favorable in the G group than in the PC/G group. Patients with wild-type EGFR tended to show greater improvement in tumor-related LCSS symptoms with chemotherapy than with gefitinib alone. These LCSS outcomes provide further evidence that patients with wild-type EGFR might not benefit from first-line treatment of advanced NSCLC with gefitinib.

A randomized Phase 3 study comparing first-line pemetrexed plus cisplatin followed by gefitinib maintenance (PC/G) with gefitinib monotherapy (G) in East Asian patients (pts) with locally advanced or metastatic nonsquamous non-small cell lung cancer (nSqNSCLC): Final survival results.

8041 Background: The primary analysis of this open-label, randomized, multicenter study found no significant difference in progression-free survival (PFS) between PC/G and G in pts with nSqNSCLC and unknown epidermal growth factor receptor (EGFR) mutation status, although the unadjusted hazard ratio (HR, PC/G vs G) favored PC/G (0.85, 95% CI: 0.63–1.13). Final overall survival (OS) data are reported here. Methods: Eligible pts were chemonaive, East Asian light ex-smokers/never-smokers aged ≥18 years with advanced nSqNSCLC, ECOG PS 0/1 and unknown EGFR mutation status. Pts (N = 236) were randomized (1:1) to PC/G (pemetrexed 500 mg/m2 + cisplatin 75 mg/m2for six 21-day cycles then gefitinib 250 mg/day) or G (gefitinib 250 mg/day). EGFR mutation status was determined for 76 pts; 52 (68.4%) had mutations. OS was analyzed (intent-to-treat population) by unadjusted Cox regression analysis. Results: Baseline characteristics were similar between groups (both N = 118). Median OS was similar in the PC/G and G group...

Gefitinib maintenance therapy in Chinese advanced-stage lung adenocarcinoma patients with EGFR mutations treated with prior chemotherapy.

The aim of this study was to determine the response of advanced-stage non-small cell lung cancer (NSCLC) patients with or without EGFR mutations to platinum-based chemotherapy with or without gefitinib maintenance. Patients were treated with four cycles of platinum-based chemotherapy. Patients with wild-type EGFR were observed (group 1; n=15). EGFR mutation-positive patients were randomly assigned to observation (group 2; n=7) or gefitinib maintenance (group 3; n=7). The median patient age was 59 years. The 1-year progression-free survival rates in groups 1, 2, and 3 were 6.7%, 28.6%, and 57.1%, respectively (p = 0.049); the 1-year overall survival rates were 53.3%, 57.1 %, and 100%, respectively (p = 0.111). The results indicate that patients with advanced-stage NSCLC with EGFR mutations have abetter response to chemotherapy followed by gefitinib than chemotherapy alone and abetter response to chemotherapy than wild-type patients. chemotherapy, gefitinib, NSCLC, tyrosine kinase inhibitors.

High efficacy of gefitinib in the treatment of EGFR mutation-positive advanced non-small cell lung adenocarcinoma: A case report.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, are known to play a significant role in EGFR mutation-positive non-small cell lung cancer. When an EGFR mutation is found, gefitinib and erlotinib have been shown to have significant roles in the treatment of untreated advanced NSCLC. This study reports an EGFR mutation in NSCLC treated with gefitinib and is notable due to the patient’s marked improvement following a shorter than average duration of treatment with gefitinib. The present study reports the case of a 58-year-old male smoker with a dry cough. Computed tomography revealed a mass in the left inferior lobe of the lung. The patient was subsequently diagnosed with advanced lung adenocarcinoma, and an EGFR mutation (in-frame deletions of E746-A750 in exon 19) was found. The patient received multiple rounds of chemotherapy, followed by gefitinib maintenance therapy for 3 months. Later on, a grade 1 acne-like rash developed on the face and back that lasted throughout the treatment. Currently, the patient is stable, with no evidence of disease progression. The present study describes the disease and the treatment using gefitinib.

First-line pemetrexed plus cisplatin followed by gefitinib maintenance therapy versus gefitinib monotherapy in East Asian patients with locally advanced or metastatic non-squamous non-small cell lung cancer: A randomised, phase 3 trial

BackgroundIn the Iressa Pan-ASia Study (IPASS), gefitinib claimed improved progression-free survival (PFS) versus carboplatin-paclitaxel in clinically selected lung cancer patients. The primary objective of this study was to assess the PFS of pemetrexed-cisplatin (PC) followed by gefitinib maintenance versus gefitinib monotherapy in an IPASS-like population. MethodsIn this open-label, randomised, phase 3 trial, eligible patients were ⩾18years, chemonaïve, East Asian, light ex-smokers/never-smokers with advanced non-squamous non-small cell lung cancer, an Eastern Cooperative Oncology Group (ECOG) performance status 0–1 and unknown epidermal growth factor receptor (EGFR) mutation status who enrolled at 12 sites in Asia. Patients randomly received (1:1) pemetrexed (500mg/m2) plus cisplatin (75mg/m2) for six 21-day cycles, followed by gefitinib maintenance or gefitinib monotherapy (250mg/day). Patient tissue was retrospectively analysed for EGFR mutations. This study is registered with ClinicalTrials.gov, NCT01017874. FindingsBetween 23rd November 2009 and 27th April 2012, 253 patients entered, and 236 patients were randomly assigned to and treated with PC therapy (N=114) and gefitinib monotherapy (N=118). Between-arm baseline characteristics were balanced. PFS was not significantly different between treatment arms (p=0.217). The unadjusted hazard ratio (HR) was 0.85 (95% confidence interval (CI) 0.63–1.13). The HR should be cautiously interpreted as it was not constant. EGFR mutation status was determined for 74 tissue samples; 50 (67.6%) had mutations. In a pre-specified subgroup analysis, only the treatment-by-EGFR mutation interaction was significant (p=0.008) for PFS. For the entire treatment period, a higher proportion of patients in the PC/gefitinib arm versus gefitinib experienced possibly drug-related grade 3–4 treatment-emergent adverse events (39 of 114 [34%] versus 19 of 118 [16%]; p=0.002). InterpretationIn the intention-to-treat (ITT) population, PFS was not significantly different. In the biomarker-assessable population, front-line EGFR tyrosine kinase inhibitor monotherapy was not efficacious in patients with wild-type EGFR. Identification of EGFR mutation status is key in the management of advanced non-squamous non-small cell lung cancer. FundingEli Lilly and Company.

P0066 A randomised phase 3 study comparing first-line pemetrexed plus cisplatin followed by gefitinib as maintenance with gefitinib monotherapy in east Asian patients with locally advanced or metastatic non-squamous non-small cell lung cancer

<h3>Background</h3> The IPASS study reported that gefitinib provided superior progression-free survival (PFS) compared with carboplatin and paclitaxel in a clinically selected lung cancer patient population; the benefit was restricted to patients with epidermal growth factor receptor gene (EGFR)-mutant tumours because patients with wild-type (WT) tumours had inferior outcomes. The current study compared PFS for pemetrexed plus cisplatin induction therapy followed by gefitinib as maintenance therapy versus gefitinib monotherapy as first-line treatments in patients with non-squamous non-small cell lung cancer. <h3>Methods</h3> Patients (<i>n</i>=236) with unknown EGFR mutation status were randomised 1:1 to pemetrexed plus cisplatin for six cycles or gefitinib. Patients without progressive disease after six cycles received gefitinib maintenance therapy. Primary endpoint analysis (Wilcoxon test after 169 PFS events) provided 80% power if the true hazard ratio (HR) was 0.65. Tissue samples were analysed for EGFR mutation status. <h3>Findings</h3> Baseline characteristics were balanced across treatment arms. 50 (68%) of 74 samples had mutations. Primary PFS analysis showed no significant difference between treatment arms (Wilcoxon <i>p</i>= 0.217). Unadjusted HR was 0.85 (95% confidence interval [CI] 0.63–1.13). During most of the study, the Kaplain Meier curve for pemetrexed plus cisplatin remained above the curve for gefitinib. In a prespecified subgroup analysis, EGFR-by-treatment interaction was statistically significant (<i>p</i>=0.008), showing treatment effect significantly differed by EGFR status. The PFS HR favoured pemetrexed plus cisplatin in EGFR-mutated and EGFR-WT patients, but the magnitude of benefit was greater in EGFR-WT patients (EGFR-mutated: HR 0.83 [95% CI 0.42–1.62], <i>p</i>=0.585; EGFR-WT: HR 0.18 [95% CI 0.06–0.51], <i>p</i>=0.001). HRs for intention to treat (ITT) and EGFR-mutated patients were not constant and should be interpreted with caution. <h3>Interpretation</h3> In the ITT population, the PFS difference was not statistically significant. In the biomarker assessable population, EGFR-WT patients did not benefit from front-line EGFR tyrosine kinase inhibitor treatment. Identification of EGFR mutational status is key for management of advanced non-squamous non-small cell lung cancer.

A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer

Current pemetrexed/platinum chemotherapy does not produce a satisfactory therapeutic response in advanced lung cancer patients. The aim of this study was to determine whether the administration of gefitinib, a tyrosine kinase inhibitor (TKI), intercalated with pemetrexed/platinum could improve the efficacy in chemotherapy-naïve patients with advanced non-squamous NSCLC without subsequent gefitinib maintenance therapy. Treatment-naïve patients with stage IIIB or IV NSCLC were randomly assigned to receive pemetrexed (500 mg/m2 d1) and either cisplatin (75 mg/m2 d1) or carboplatin (AUC = 5 d1) plus gefitinib (250 mg/d on days 3 to 16 of a 3-week cycle) (PC-G) or pemetrexed–platinum (PC) alone. Randomization was stratified according to the tobacco smoking status and EGFR mutational status of the patients. The primary endpoint was the non-progression rate (NPR) at 12 weeks. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and biosafety. The NPR at 12 weeks was 84.5% for the PC-G treatment arm and 83.1% for the PC treatment arm (P = 0.87). Median PFS was 7.9 months for the PC-G arm and 7.0 months for the PC arm (P = 0.57). The ORR was 50.0% for the PC-G arm and 47.4% for the PC arm (P = 0.78). Median survival was 25.4 mo for the PC-G arm and 20.8 mo for the PC arm (P = 0.54). The incidence of adverse events was similar between the two treatment arms, except for a higher incidence of skin rash with PC-G. Predefined subgroup analyses demonstrated that PC-G significantly increased the PFS compared with the PC regimen in patients with EGFR mutations (P = 0.017). Although gefitinib intercalated with pemetrexed/platinum chemotherapy did not improve the NPR at 12 weeks compared with chemotherapy, an improvement in the PFS for the intercalated treatment arm was seen in the subgroup of patients with EGFR mutations.