Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study.

BACKGROUND: Osimertinib (AZD9291) is an oral, potent, irreversible EGFR tyrosine-kinase inhibitor selective for EGFR tyrosine-kinase inhibitor sensitising mutations, and the EGFR Thr790Met resistance mutation. We assessed the efficacy and safety of osimertinib in patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), who had progressed after previous therapy with an approved EGFR tyrosine-kinase inhibitor. METHODS: In this phase 2, open-label, single-arm study (AURA2), patients aged at least 18 years with centrally confirmed EGFR Thr790Met-positive mutations, locally advanced or metastatic (stage IIIB/IV) NSCLC who progressed on previous EGFR tyrosine-kinase inhibitor therapy received osimertinib 80 mg orally once daily; treatment could continue beyond progression if the investigator observed a clinical benefit. Patients with asymptomatic, stable CNS metastases not requiring steroids were allowed to enrol. The primary endpoint was the proportion of patients achieving an objective response by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1. Response endpoints were assessed in the evaluable for response analysis set (ie, all patients who received at least one dose of osimertinib and had measurable disease at baseline according to blinded independent central review). Other endpoints and safety were assessed in all patients receiving at least one osimertinib dose (full analysis set). The study is ongoing and patients are still receiving treatment. This study is registered with ClinicalTrials.gov, number NCT02094261. FINDINGS: Between May 20, 2014, and Sept 12, 2014, 472 patients were screened, of whom 210 started osimertinib treatment between June 13, 2014, and Oct 27, 2014; 11 patients were excluded from the evaluable for response analysis set (n=199) due to absence of measurable disease at baseline by blinded independent central review. At data cutoff (Nov 1, 2015), 122 (58%) patients remained on treatment. The median duration of follow-up was 13·0 months (IQR 7·6-14·2). 140 (70%; 95% CI 64-77) of 199 patients achieved an objective response by blinded independent central review: confirmed complete responses were achieved in six (3%) patients and partial responses were achieved in 134 (67%) patients. The most common all-causality grade 3 and 4 adverse events were pulmonary embolism (seven [3%]), prolonged electrocardiogram QT (five [2%]), decreased neutrophil count (four [2%]), anaemia, dyspnoea, hyponatraemia, increased alanine aminotransferase, and thrombocytopenia (three [1%] each). Serious adverse events were reported in 52 (25%) patients, of which 11 (5%) were investigator assessed as possibly treatment-related to osimertinib. Seven deaths were due to adverse events; these were pneumonia (n=2), pneumonia aspiration (n=1), rectal haemorrhage (n=1), dyspnoea (n=1), failure to thrive (n=1), and interstitial lung disease (n=1). The only fatal event assessed as possibly treatment-related by the investigator was due to interstitial lung disease. INTERPRETATION: Osimertinib showed clinical activity with manageable side-effects in patients with EGFR Thr790Met-positive NSCLC. Therefore, osimertinib could be a suitable treatment for patients with EGFR Thr790Met-positive disease who have progressed on an EGFR tyrosine-kinase inhibitor. FUNDING: AstraZeneca.

Head and Neck Cancers, Version 1.2015.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.

Dacomitinib as first-line treatment in patients with clinically or molecularly selected advanced non-small-cell lung cancer: a multicentre, open-label, phase 2 trial.

BACKGROUND: Patients with EGFR-mutant non-small-cell lung cancer generally have a progression-free survival of 9-13 months while being treated with the EGFR tyrosine-kinase inhibitors gefitinib or erlotinib. However, resistance inevitably develops, and more effective EGFR inhibitors are needed. Dacomitinib is a covalent pan-HER inhibitor that has shown clinical activity in patients previously treated with gefitinib or erlotinib. We did a trial of dacomitinib as initial systemic therapy in clinically and molecularly selected patients with advanced non-small-cell lung cancer. METHODS: In this open-label, multicentre, phase 2 trial, we enrolled treatment-naive patients with advanced lung cancer who had clinical (never-smokers [<100 cigarettes per lifetime] or former light smokers [<10 pack-years per lifetime] and ≥15 years since last cigarette) or molecular (EGFR mutation, regardless of smoking status) characteristics associated with response to EGFR inhibitors. We gave dacomitinib orally once daily (45 mg or 30 mg) until progressive disease, unacceptable toxicity, or patient withdrawal. We used Response Evaluation Criteria in Solid Tumors criteria (version 1.0) to investigate the activity of dacomitinib in all patients with a baseline scan and at least one post-treatment scan, with investigator assessment of response and progression. The primary endpoint was progression-free survival at 4 months in the as-enrolled population, with a null hypothesis of progression-free survival at 4 months of 50% or less. The study is registered with ClinicalTrials.gov, number NCT00818441, and is no longer accruing patients. FINDINGS: Between March 11, 2009, and April 1, 2011, we enrolled 89 patients from 25 centres, including 45 (51%) with EGFR-activating mutations in exon 19 (n=25) or exon 21 (n=20). Progression-free survival at 4 months was 76·8% (95% CI 66·4-84·4) in the as-enrolled population, and was 95·5% (95% CI 83·2-98·9) in the EGFR-mutant population. The most common all-grade treatment-related adverse events were diarrhoea in 83 (93%) patients, dermatitis acneiform in 69 (78%) patients, dry skin in 39 (44%) patients, and stomatitis in 36 (40%) patients. Two patients (2%) had grade 4 treatment-related events (one with hypokalaemia and one with dyspnoea). No grade 5 toxicities were recorded. INTERPRETATION: Dacomitinib had encouraging clinical activity as initial systemic treatment in clinically or molecularly selected patients with advanced non-small-cell lung cancer. FUNDING: Pfizer.

Head and neck cancers, Version 2.2014. Clinical practice guidelines in oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."

Head and neck cancers, version 2.2013. Featured updates to the NCCN guidelines.

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).

Immune Activation in Early-Stage Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab.

Purpose: To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early-stage non-small cell lung cancer (NSCLC) patients.Experimental Design: This is a single-arm chemotherapy plus phased ipilimumab phase II study of 24 treatment-naïve patients with stage IB-IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles.Results: Chemotherapy alone had little effect on immune parameters in PBMCs. Profound CD28-dependent activation of both CD4 and CD8 cells was observed following ipilimumab. Significant increases in the frequencies of CD4+ cells expressing activation markers ICOS, HLA-DR, CTLA-4, and PD-1 were apparent. Likewise, increased frequencies of CD8+ cells expressing the same activation markers, with the exception of PD-1, were observed. We also examined 7 resected tumors and found higher frequencies of activated tumor-infiltrating lymphocytes than those observed in PBMCs. Surprisingly, we found 4 cases of preexisting tumor-associated antigens (TAA) responses against survivin, PRAME, or MAGE-A3 present in PBMC at baseline, but neither increased frequencies nor the appearance of newly detectable responses following ipilimumab therapy. Ipilimumab had little effect on the frequencies of circulating regulatory T cells and MDSCs.Conclusions: This study did not meet the primary endpoint of detecting an increase in blood-based TAA T-cell responses after ipilimumab. Collectively, these results highlight the immune activating properties of ipilimumab in early-stage NSCLC. The immune profiling data for ipilimumab alone can contribute to the interpretation of immunologic data from combined immune checkpoint blockade immunotherapies. Clin Cancer Res; 23(24); 7474-82. ©2017 AACR.

Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury.

PURPOSE: Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy. METHODS AND MATERIALS: Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status>or=70, and life expectancy>or=6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m2) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria. RESULTS: Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed. CONCLUSIONS: The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity.

Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer.

To determine the feasibility and toxicity of radiation therapy, delivered either as definitive treatment or following surgery, following neo-adjuvant immune checkpoint inhibition for locally advanced NSCLC sixteen patients who received neo-adjuvant chemotherapy including ipilimumab as part of a phase II study were identified. Patients were analyzed by intent of radiation and toxicity graded based on CTCAE 4.0. There were seven patients identified who received definitive radiation and nine who received post-operative radiation. There was no grade 3 or greater toxicity in the definitive treatment group although one patient stopped treatment early due to back pain secondary to progression outside of the treatment field. In the post-operative treatment group, one patient required a one week break due to grade 2 odynophagia and no grade 3 or greater toxicity was observed. In this study of radiation as definitive or post-operative treatment following neo-adjuvant chemotherapy including ipilimumab for locally advanced NSCLC was feasible and well tolerated with limited toxicity.

Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer.

PURPOSE: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. METHODS AND MATERIALS: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standard 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. RESULTS: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). CONCLUSIONS: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.

Microvessel density in advanced head and neck squamous cell carcinoma before and after chemotherapy.

OBJECTIVE: Studies of tumor angiogenesis in head and neck squamous cell carcinoma (HNSCC) in regard to correlation with prognostic significance have yielded inconclusive results. To determine whether the microvessel density (MVD) within the tumor of advanced (Stages III and IV) HNSCC has any impact on tumor response to 2-3 courses of paclitaxel (Taxol) and carboplatin, we prospectively studied pre-chemotherapy specimens from patients with previously untreated, advanced stage HNSCC. We also attempted to study residual tumors after chemotherapy to determine if the MVD within the tumor had changed. STUDY DESIGN: The MVD within the tumor was obtained by immunohistochemical staining of the tumors with Q-Bend 10 (CD34). The "hot-spot" areas of each tumor (ie., areas with most intense blood neovascularization) were considered for evaluation. Results were expressed as the Average number of microvessels identified in 5-400x microscope fields (ie., the number of microvessels counted in 5-400x microscope fields divided by 5). SETTING: Tertiary University Medical Center. INTERVENTION: Two to 3 courses of chemotherapy with paclitaxel and carboplatin. MAIN OUTCOME MEASURES: Progression-free and overall survival with 5 years follow-up, RESULTS: The tumoral MVD in 32 HNSCC specimens before chemotherapy ranged from 4.0-39.0 (mean, 14.8; median, 14.2). Eight out of 32 patients achieved pathologically complete remission; their tumoral MVD revealed a mean of 10.9. The 24 remaining patients had pathologically-confirmed residual tumor post-chemotherapy; their tumoral MVD revealed a mean of 16.5. CONCLUSION: Statistical analyses revealed no evidence of a relationship between remission and a MVD > or < 10 or > or < 16.5. There was no correlation of tumoral MVD with overall or progression-free survival. In 15 patients, tumoral MVD results were also available on the post-chemotherapy specimens. The greater the difference of the tumoral MVD between the pre- and post-chemotherapy specimens, the shorter the patients overall and progression-free survival (p = 0.042).

The role of intratumoral therapy with cisplatin/epinephrine injectable gel in the management of advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: To determine the safety and efficacy of targeted antitumor therapy with cisplatin/epinephrine injectable gel in patients with advanced squamous cell carcinoma of the head and neck. DESIGN: Two prospective, double-blind, placebo-controlled phase III trials of identical design. Crossover from blinded to open-label phase was permitted for patients with disease progression. SETTING: Tertiary referral centers in North America and Europe. PATIENTS: One hundred seventy-nine intensively pretreated patients with recurrent or refractory squamous cell carcinoma of the head and neck. INTERVENTION: Cisplatin/epinephrine injectable or placebo gel was administered by direct intratumoral injection; up to 6 weekly treatments. Dose was 0.25 mL of active or placebo gel per cubic centimeter of tumor up to 10 mL total. Patient benefit after local tumor control of the most symptomatic tumor was assessed by patients and physicians using the Treatment Goals Questionnaire. MAIN OUTCOME MEASURES: Local tumor response and patient benefit attributable to improvements in tumor-related symptoms. RESULTS: Combined results for the 178 patients with evaluable data in the 2 trials confirmed objective tumor responses in 35 (29%) of 119 patients, including 23 (19%) complete responses achieved with cisplatin/epinephrine gel, vs 1 (2%) of 59 for placebo (P<.001). Tumor response and patient benefit were significantly correlated (P=.006): 47% (17/36) of patients with target tumor responses achieved a rigorously defined benefit based on a prospectively selected treatment goal vs 15% (22/142) of nonresponders. CONCLUSION: Cisplatin/epinephrine injectable gel reduces tumor burden, ameliorates tumor symptoms, and provides a new therapeutic option for treating patients with squamous cell carcinoma of the head and neck.

Metallopanstimulin as a marker for head and neck cancer.

BACKGROUND: Metallopanstimulin (MPS-1) is a ribosomal protein that is found in elevated amounts in the sera of patients with head and neck squamous cell carcinoma (HNSCC). We used a test, denoted MPS-H, which detects MPS-1 and MPS-1-like proteins, to determine the relationship between MPS-H serum levels and clinical status of patients with, or at risk for, HNSCC. PATIENTS AND METHODS: A total of 125 patients were prospectively enrolled from a university head and neck oncology clinic. Participants included only newly diagnosed HNSCC patients. Two control groups, including 25 non-smokers and 64 smokers, were studied for comparison. A total of 821 serum samples collected over a twenty-four month period were analyzed by the MPS-H radioimmunoassay. RESULTS: HNSCC, non-smokers, and smokers had average MPS-H values of 41.5 ng/mL, 10.2 ng/mL, and 12.8 ng/mL, respectively (p = 0.0001). CONCLUSION: We conclude that MPS-1 and MPS-1-like proteins are elevated in patients with HNSCC, and that MPS-H appears to be a promising marker of presence of disease and response to treatment in HNSCC patients.

Endobronchial fiducial to guide stereotactic body radiotherapy.

Optimal treatment for unresectable central airway tumors is not well established. Stereotactic body radiation therapy has shown efficacy for both peripheral and central lung lesions. However, the treatment of central tumors has been limited because of associated radiation toxicity. We report the use of an endobronchial fiducial to localize hypofractionated stereotactic body radiation therapy treatment of a limited central airways disease in a patient with recurrent metastatic squamous cell lung cancer. The fiducial was instrumental in designing the treatment field and minimizing related treatment toxicity. Future studies may take advantage of this technique in patients with unresectable central airways non-small cell lung cancers.

A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma.

INTRODUCTION: Malignant mesothelioma (MM) cells express the vascular endothelial growth factor (VEGF) receptor, and VEGF protein expression is detected in a majority of human mesothelioma biopsy specimens. Bevacizumab is a recombinant humanized monoclonal antibody that blocks the binding of VEGF to its receptor. We evaluated the addition of bevacizumab to cisplatin and pemetrexed as first-line treatment in patients with advanced, unresectable MM. METHODS: Previously untreated MM patients with advanced, unresectable disease received cisplatin (75 mg/m(2)), pemetrexed (500 mg/m(2)), and bevacizumab (15 mg/kg) intravenously every 21 days for a maximum of 6 cycles. Patients with responsive or stable disease received bevacizumab (15 mg/kg) intravenously every 21 days until progression or intolerance. The primary endpoint was progression-free survival rate at 6 months. RESULTS: 53 patients were enrolled at 4 centers; 52 were evaluable for this analysis. The progression-free survival rate at 6 months was 56% and the median progression-free survival was 6.9 months (95% confidence interval [CI], 5.3-7.8 months). The partial response rate was 40% and 35% of patients had stable disease. Median overall survival was 14.8 months (95% CI; 10.0-17.0 months). Grade 3/4 toxicities included neutropenia in 11%, hypertension in 6%, and venous thromboembolism in 13% of patients. CONCLUSION: This trial evaluating the addition of bevacizumab to cisplatin and pemetrexed in patients with previously untreated, advanced MM failed to meet the primary endpoint of a 33% improvement in the progression-free survival rate at 6 months compared with historical controls treated with cisplatin and pemetrexed alone.

Prospective trial of synchronous bevacizumab, erlotinib, and concurrent chemoradiation in locally advanced head and neck cancer.

PURPOSE: We assessed the safety and efficacy of synchronous VEGF and epidermal growth factor receptor (EGFR) blockade with concurrent chemoradiation (CRT) in locally advanced head and neck cancer (HNC). EXPERIMENTAL DESIGN: Newly diagnosed patients with stage III/IV HNC received a 2-week lead-in of bevacizumab and/or erlotinib, followed by both agents with concurrent cisplatin and twice daily radiotherapy. Safety was assessed using Common Toxicity Criteria version 3.0. The primary efficacy endpoint was clinical complete response (CR) rate after CRT. RESULTS: Twenty-nine patients enrolled on study, with 27 completing therapy. Common grade III toxicities were mucositis (n = 14), dysphagia (n = 8), dehydration (n = 7), osteoradionecrosis (n = 3), and soft tissue necrosis (n = 2). Feeding tube placement was required in 79% but no patient remained dependent at 12-month posttreatment. Clinical CR after CRT was 96% [95% confidence interval (CI), 82%-100%]. Median follow-up was 46 months in survivors, with 3-year locoregional control and distant metastasis-free survival rates of 85% and 93%. Three-year estimated progression-free survival, disease-specific survival, and overall survival rates were 82%, 89%, and 86%, respectively. Dynamic contrast enhanced MRI (DCE-MRI) analysis showed that patients who had failed had lower baseline pretreatment median K(trans) values, with subsequent increases after lead-in therapy and 1 week of CRT. Patients who did not fail had higher median K(trans) values that decreased during therapy. CONCLUSIONS: Dual VEGF/EGFR inhibition can be integrated with CRT in locally advanced HNC, with efficacy that compares favorably with historical controls albeit with an increased risk of osteoradionecrosis. Pretreatment and early DCE-MRI may prospectively identify patients at high risk of failure.

Phase II randomized study of dose-dense docetaxel and cisplatin every 2 weeks with pegfilgrastim and darbepoetin alfa with and without the chemoprotector BNP7787 in patients with advanced non-small cell lung cancer (CALGB 30303).

INTRODUCTION: We investigated dose-dense docetaxel and cisplatin in patients with measurable non-small cell lung cancer in a randomized phase II study without [A] or with [B] a putative chemoprotective agent, BNP7787. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB (effusion) or IV, performance status 0 to 1, and adequate organ function were eligible. Treatment with docetaxel 75 mg/m followed by cisplatin 75 mg/m over 1 hour day 1 with darbepoetin 200 mug day 1 and pegfilgrastim 6 mg day 2 without/with BNP7787 before cisplatin was repeated every other week for up to 6 cycles. The primary end point was to differentiate between grade >/=2 neurotoxicity rates of 30% on [A] and 10% on [B]. Feasibility was prospectively defined as febrile neutropenia in <10% of patients and /=2 occurred in 32% on [A] and 29% on [B]. The incidence of febrile neutropenia was 4% on [A] and 3% on [B]. Treatment delays occurred in 13% and 20% of patients on [A] and [B], respectively. Completion rates for 3/6 cycles were 84%/51% on [A] and 84%/53% on [B]. Objective response rates were 55% on [A] and 51% on [B]. Median progression-free/overall survival times were 5.5/10.7 on [A] and 6.5/14.1 month on [B]. CONCLUSIONS: This dose-dense treatment regimen is active, feasible, and tolerable. Its further investigation in the curative setting in non-small cell lung cancer should be considered. BNP7787 did not result in significant protection from neurotoxicity.

A phase II trial of carboplatin/vinorelbine with pegfilgrastim support for the treatment of patients with advanced non-small cell lung cancer.

INTRODUCTION: The impact of chemotherapy dose delivery has not been well studied in patients with non-small cell lung cancer (NSCLC). Overlapping hematologic toxicities commonly limit planned dose intensity of combination chemotherapy regimens. A phase II study investigating carboplatin and vinorelbine, supported by pegfilgrastim, in the treatment of patients with advanced NSCLC was performed. METHODS: Chemotherapy-naïve patients with locally advanced or metastatic NSCLC were treated with carboplatin area under the curve (AUC) 6 mg/ml per minute intravenously on day 1 and vinorelbine 30 mg/m2 intravenously on days 1 and 8 every 3 weeks for four planned cycles. Pegfilgrastim was administered on day 9 of each cycle as a 6-mg subcutaneous injection. The primary endpoint was incidence of cycle 1 febrile neutropenia. Secondary endpoints included incidence of grade 3/4 hematologic and nonhematologic toxicities, delivered dose intensity, and overall survival. RESULTS: Thirty patients (21 men, 9 women) with a median age of 61 years (range, 43-79) were enrolled. Of 120 planned patient cycles, 101 (84%) were completed. There was one episode of cycle 1 febrile neutropenia. Overall response rate was 27%. Median dose delivered for vinorelbine was 17.2 mg/m2 per week, representing a delivered dose intensity of 86%. Median survival was 9.4 months (95% confidence interval: 6.1-18.0) with a 3-year survival rate of 20%. CONCLUSIONS: This regimen of carboplatin and vinorelbine with pegfilgrastim support was associated with a low rate of febrile neutropenia and good maintenance of planned dose intensity. Although response and survival are similar to other chemotherapy regimens in advanced NSCLC, studies optimizing chemotherapy delivery in this setting may help inform treatment approaches in patients with earlier stage disease.