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

AbstractObjectivesThe 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

Autologous dendritic cell transplantation as an adjuvant treatment in pleomorphic lung carcinoma

We embarked on autologous dendritic cells (DC) transplantation as an adjuvant therapy with chemotherapy in a pleomorphic lung carcinoma patient. DC were isolated from PBMC and primed with the autologous tumor lysate. No adverse event was noted in DC transplantation. DC administration also correlated with immunomodulation, as evidenced by an approximately 5-fold increase in serum interferon gamma after 2 months. The utility of autologous DC transplantation may offer a clinical benefit with virtually no adverse event

N‑Glycan and Glycopeptide Serum Biomarkers in Philippine Lung Cancer Patients Identified Using Liquid Chromatography–Tandem Mass Spectrometry

Aberrant glycosylation has been extensively reported in cancer, with fundamental changes in the glycosylation patterns of cell-surface and secreted proteins largely occurring during cancer progression. As such, serum glycan and glycopeptide biomarkers have been discovered using mass spectrometry and proposed for cancer detection. Here, we report for the first time potential serum N-glycan and glycopeptide biomarkers for Philippine lung cancer patients. The N-glycan and glycoprotein profiles of a cohort (n = 26 patients, n = 22 age- and gender-matched) of lung cancer patients were analyzed and compared to identify potential N-glycan and glycopeptide serum biomarkers using nano-QToF-MS/MS and ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry dynamic multiple monitoring methods, respectively. Statistical analyses identified differential N-glycan and glycopeptide abundances. The N-glycans were mostly sialylated and sialofucosylated branched structures. The glycopeptides involved proteins in complement and coagulation cascades (p adj = 6.418 × 10-4), innate immunity (p adj = 6.094 × 10-3), acute inflammatory response (p adj = 6.404 × 10-5), defense response (p adj = 2.082 × 10-4), complement activation pathways (p adj = 1.895 × 10-2), and immunoglobulin-mediated immune response pathways (p adj = 4.818 × 10-2). Biomarker models were constructed using serum N-glycans [area under the curve (AUC) = 0.775; 95% CI: 0.617-0.931] and glycopeptides (AUC = 0.959; 95% CI: 0.85-1.0), with glycopeptides having higher accuracies than N-glycans. The results suggest that in the Philippine lung cancer patient sera, specific N-glycans and site-specific glycans are differentially expressed between cases and controls. This report represents the first serum glycan and glycopeptide biomarkers of Philippine lung cancer patients, further demonstrating the utility of mass spectrometry-based glycomic and glycoproteomic methods

Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study

International audiencehas a patent T-cell immunotherapy development pending; is a founder and owner of BioCytics, which is a clinical research laboratory developing T-cell immunotherapy; and has previously bought stock in the T-cell companies LionBiotech, Juno, Blue Bird, Kite Pharma, and ZioPharm. CC has received fees during the past 5 years for attending scientific meetings, speaking, organising research, and providing consulting services from AstraZeneca

Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC

BACKGROUND: Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported. METHODS: In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point. RESULTS: The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P = 0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group. CONCLUSIONS: Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.).status: publishe