Saulius Cicenas

Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study

BACKGROUND First-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) is usually limited to four to six cycles. Maintenance therapy can delay progression and prolong survival. The oral epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib has proven efficacy and tolerability in second-line NSCLC. We designed the phase 3, placebo-controlled Sequential Tarceva in Unresectable NSCLC (SATURN; BO18192) study to assess use of erlotinib as maintenance therapy in patients with non-progressive disease following first-line platinum-doublet chemotherapy. METHODS Between December, 2005, and May, 2008, 1949 patients were included in the run-in phase (four cycles of platinum-based chemotherapy). At the end of the run-in phase, 889 patients who did not have progressive disease were entered into the main study, and were randomly allocated using a 1:1 adaptive randomisation method through a third-party interactive voice response system to receive erlotinib (150 mg/day; n=438) or placebo (n=451) until progression or unacceptable toxicity. Patients were stratified by EGFR immunohistochemistry status, stage, Eastern Cooperative Oncology Group performance status, chemotherapy regimen, smoking history, and region. Co-primary endpoints were progression-free survival (PFS) in all analysable patients irrespective of EGFR status, and PFS in patients whose tumours had EGFR protein overexpression, as determined by immunohistochemistry. This study is registered with www.ClinicalTrials.gov, number NCT00556712. FINDINGS 884 patients were analysable for PFS; 437 in the erlotinib group and 447 in the placebo group. After a median follow-up of 11.4 months for the erlotinib group and 11.5 months for the placebo group, median PFS was significantly longer with erlotinib than with placebo: 12.3 weeks for patients in the erlotinib group versus 11.1 weeks for those in the placebo group (HR 0.71, 95% CI 0.62-0.82; p<0.0001). PFS was also significantly longer in patients with EGFR-positive immunohistochemistry who were treated with erlotinib (n=307) compared with EGFR-positive patients given placebo (n=311; median PFS 12.3 weeks in the erlotinib group vs 11.1 weeks in the placebo group; HR 0.69, 0.58-0.82; p<0.0001). The most common grade 3 or higher adverse events were rash (37 [9%] of 443 patients in the erlotinib group vs none of 445 in the placebo group) and diarrhoea (seven [2%] of 443 patients vs none of 445). Serious adverse events were reported in 47 patients (11%) on erlotinib compared with 34 patients (8%) on placebo. The most common serious adverse event was pneumonia (seven cases [2%] with erlotinib and four [<1%] with placebo). INTERPRETATION Maintenance therapy with erlotinib for patients with NSCLC is well tolerated and significantly prolongs PFS compared with placebo. First-line maintenance with erlotinib could be considered in patients who do not progress after four cycles of chemotherapy. FUNDING F Hoffmann-La Roche Ltd.

The role of genetic and other biomarkers in NSCLC prognosis

The development of non-small-cell lung cancer (NSCLC) is a multistep process, which is triggered and maintained by various factors. Many steps of non-small-cell lung carcinogenesis, risk factors and biomarkers have been identified; however no consistent model has been established of personalized medicine for these patients. Distinct various gene expression, products of mutated genes and other markers such as circulating nucleic acids or tumor cells has been proven to be potential biomarkers of non-small cell lung cancer as well as potential targets for new treatment strategies. This article will highlight promising biomarkers in non-small cell lung cancer prognosis.

Suicide risk among lung cancer patients in Lithuania

Several large cancer registry data based studies have demonstrated an increased risk of suicide among cancer patients compared with the general population.[1] The majority of studies reported that cancers of the lung generally carry the highest rates of patient suicides. In this study, we explored whether suicide risk is affected by a lung cancer diagnosis among cancer patients in Lithuania in relation to demographic patients and tumour characteristics and time since diagnosis. 19 781 primary lung cancer cases (16 620 men and 3 161 women) diagnosed between 1998 and 2012 were included in the analysis. This article is protected by copyright. All rights reserved.

Primary malignant peripheral nerve sheath tumour of the heart

A malignant peripheral nerve sheath tumour (MPNST) is a rare variety of soft-tissue sarcoma of ectomesenchymal origin. The World Health Organisation created the term MPNST to replace previous terminology such as malignant schwannoma, malignant neurilemmoma, neurogenic sarcoma, and myxofibrosarcoma for tumours of neurogenic origin with similar biological behavior.[1–3] The vast majority of these tumours develop in extremities. They also tend to be located in unusual sites of the body, such as the pelvic retroperitoneum, infratemporal fossa, intrapericardium, and mediastinum.[1,3,4] This case study presents a patient with an extremely rare primary cardiac MPNST..

88PD EFFICACY AND SAFETY OF ERLOTINIB VERSUS CHEMOTHERAPY IN SECOND-LINE ADVANCED NON-SMALL-CELL LUNG CANCER (NSCLC) WITH POOR PROGNOSIS: THE PHASE III TITAN STUDY

Background: Erlotinib (E), docetaxel (D) and pemetrexed (P) are all approved in the second-line setting for patients (pts) with advanced NSCLC who progress following first-line platinum doublet chemotherapy (PDC), but head-to-head data from large clinical trials are limited. The multicentre, international, openlabel, phase III TITAN study investigated the efficacy and tolerability of E vs chemotherapy (D or P) as second-line therapy for NSCLC after rapid progression on first-line PDC. Methods: During initiation, 2590 chemonaive pts with advanced NSCLC received up to 4 cycles of first-line PDC. Pts with controlled disease were offered entry into the SATURN phase III study of maintenance erlotinib; those with disease progression were offered entry into TITAN (n = 424). Pts in TITAN were stratified by stage, ECOG PS, smoking history and region, and were randomised (1:1) to receive E 150mg/d or chemotherapy (either D or P, investigators’ choice; standard regimens), until toxicity or progression. Overall survival (OS) was the primary endpoint. Secondary endpoints included progression-free survival (PFS), response rate (ORR), biomarker analyses and safety. Results: Baseline characteristics were balanced between the two arms and the full analysis population comprised 203 pts for E and 221 for chemotherapy (116 for D and 105 for P). No difference in OS was seen between arms: HR = 0.96 (95% CI 0.78 1.19; log-rank p = 0.73; median 5.3 months with E vs 5.5 months with chemotherapy). Similarly, no significant difference was seen in PFS: HR = 1.19 (95% CI 0.97 1.46; log-rank p = 0.09; median 6.3 weeks with E vs 8.6 weeks with chemotherapy). Subgroup analyses will be presented. ORR was 7.9% with E vs 6.3% with chemotherapy. More treatmentrelated adverse events were seen with E (AEs; 58.2% vs 40.8% with chemotherapy), mostly grade 1/2 rash or diarrhoea. Grade 5 AEs were rare with E (1.5% vs 5.2% of pts on chemotherapy). Serious treatment-related AEs were seen in 1% of pts in the E arm vs 6.6% of those in the chemotherapy arm; withdrawal due to AEs was required in 1% and 3.8% of pts, respectively. Conclusions: Erlotinib had similar efficacy to chemotherapy in second-line advanced NSCLC, even in patients who had progressed rapidly on first-line PDC. Erlotinib was well tolerated compared with chemotherapy in this population. Disclosure: T. Ciuleanu: I have taken part in Advisory boards for Roche, Amgen, Merck, GlaxoSmithKline, Lilly, BMS, OSIP. All other authors have declared no conflicts of interest.