A model projecting outcomes for nationwide low-dose CT screening for lung cancer estimated that gradual implementation of the program would detect roughly 54,900 more cases over five years in a high-risk Medicare population. The large majority of new cases would be early-stage disease.
The model assumes that over a five-year period, an additional 20 percent of high risk patients are offered screening each year. Investigators considered three different screening use scenarios for the implementation: an expected-use scenario based on historic experience with mammography (50 percent of patients offered screening undergo screening every year), a low-use scenario (25 percent), and a high-use scenario (75 percent).
The study, funded by Genentech, will be presented June 2 at the American Society of Clinical Oncology annual meeting in Chicago.
In the expected screening use scenario, the screening would yield 11.2 million more LDCT scans over five years, compared to no screening.
It is estimated that this program would increase the proportion of early-stage diagnoses from 15 percent to 33 percent. The total five-year Medicare expenditure for LDCT imaging, diagnostic workup, and cancer care would be $9.3 billion, amounting to a $3.00-per-month premium increase for each Medicare member.
In the low- and high-screening use scenarios, the total five-year Medicare expenditure would be $5.9 and $12.7 billion, respectively.
The U.S. Preventive Services Task Force recommended LDCT largely based on findings from the National Lung Cancer Screening Trial, which demonstrated a 20 percent reduction of lung cancer deaths with LDCT screening compared to X-ray screening. Annual LDCT screening is recommended for persons age 55-80 years with a 30 pack-year smoking history who currently smoke or quit within the past 15 years.
Non-Small Cell Lung Cancer
Two Phase III Afatinib Trials Demonstrate Prolonged Survival
Two phase III clinical trials, LUX-Lung 3 and LUX-Lung 6, demonstrated that patients with advanced non-small cell lung cancer whose tumors have the most common epidermal growth factor receptor mutation lived longer if treated with first-line afatinib compared to chemotherapy.
The data will be discussed at an oral presentation at the American Society of Clinical Oncology annual meeting June 2.
In the updated, pooled analysis, afatinib (Gilotrif) prolonged survival of lung cancer patients whose tumors have common EGFR mutations compared with standard chemotherapy by a median of 3 months (24.3 to 27.3 months) and significantly reduced the risk of death by 19 percent (HR=0.81, p=0.037).
The most pronounced reduction in risk of death was 41 percent (HR=0.59, CI 0.45, 0.77) in patients whose tumors have the most common EGFR mutation, exon 19 deletion.
For patients with the exon 21 mutation there was no impact on overall survival (HR=1.25, CI 0.92, 1.71). Exon 19 deletions occur with a frequency of approximately 48 percent in EGFR-mutant lung tumors.
The progression-free survival analysis and adverse events associated with afatinib in comparison with standard chemotherapy were consistent with previously published results of the primary data from these two trials.
The LUX-Lung 3 clinical trial compared afatinib with chemotherapy (pemetrexed/cisplatin) as a first-line treatment in patients with advanced NSCLC with EGFR mutations. LUX-Lung 6 evaluated afatinib versus chemotherapy (gemcitabine/cisplatin) as a first-line treatment for Asian patients with advanced NSCLC with EGFR mutations.
A third phase III study of afatinib in NSCLC patients presented at the ASCO annual meeting, LUX-Lung 5, met its primary endpoint by showing an improvement in progression-free survival when continuing treatment with afatinib in combination with chemotherapy after the tumor started to grow on afatinib alone.
This study compared afatinib and paclitaxel versus investigator’s choice of chemotherapy alone in patients with late-stage NSCLC whose disease has progressed after afatinib alone and have also failed several treatments, including chemotherapy, erlotinib or gefitinib.
Those patients who continued afatinib treatment with the addition of chemotherapy, after progressing on afatinib alone, had a further delay in tumor growth compared to the group who stopped afatinib treatment and received chemotherapy only (tumor growth was delayed by 5.6 months and 2.8 months respectively, p=0.003). This corresponded to a 40 percent reduction in risk of disease progression (HR=0.60).
Afatinib is an oral, once-daily kinase inhibitor that is designed to irreversibly bind and inhibit EGFR (ErbB1), HER2 (ErbB2) and ErbB4. Sponsored by Boehringer Ingelheim, afatinib is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 substitution mutations as detected by an FDA-approved test.
EGFR Inhibitor Shrinks Tumors in Phase I Study of Patients with Treatment-Resistant Mutation
A phase I study of a mutant selective EGFR tyrosine kinase inhibitor demonstrated tumor shrinkage in roughly 50 percent of patients with advanced, EGFR-mutant, non-small cell lung cancer resistant to standard EGFR inhibitors.
The drug, AZD9291, worked particularly well in patients with the T790M mutation, which causes the most common form of EGFR therapy resistance. The study will be presented at the annual meeting of the American Society of Clinical Oncology in Chicago on May 31.
EGFR mutations are found in 10-15 percent of Caucasian patients and about 40 percent of Asian patients with NSCLC. Many of these patients initially respond well to approved EGFR inhibitors erlotinib and afatinib, but all ultimately become resistant to this therapy, generally within 10 to 14 months.
In the study, 199 patients with advanced NSCLC harboring EGFR mutations whose disease progressed after one or more standard EGFR therapies received different doses of AZD9291. Responses were observed at all dose levels and in all subgroups of patients, including those with brain metastasis.
Among the 89 patients with the T790M mutation, 64 percent responded to AZD9291, compared to 23 percent of T790M-negative patients. The responses were still ongoing in nearly all patients at data cut-off, with the longest response lasting more than eight months. Longer follow up is needed to determine overall survival.
AZD9291 selectively targets EGFR in tumors and appears to cause fewer skin toxicities than approved EGFR TKIs. Existing drugs block both the mutant EGFR in the tumor and the normal EGFR in the skin, often leading to debilitating skin rash or acne. The study was funded by Astra Zeneca, the drug’s sponsor.
VeriStrat Biomarker Test Predicts Treatment Outcomes in Phase III NSCLC Trial
A phase III study showed that the VeriStrat biomarker test was predictive of differential treatment outcomes between two standard treatment options for advanced non-small cell lung cancer.
The study, named PROSE, examined patients who have progressed after first-line treatments and who are EGFR wild-type or whose EGFR status is unknown, and tested between single-agent chemotherapy and Tarceva (erlotinib).
Data from the multi-center, randomized proteomic stratified study of 285 patients was published in The Lancet Oncology.
For patients whose EGFR status is unknown, VeriStrat identifies those who can still be considered for the targeted therapy. VeriStrat also helps rule out the roughly 30 percent of patients who are highly unlikely to benefit from erlotinib and should receive chemotherapy.
The VeriStrat test is sponsored by Biodesix Inc. Tarceva is a trademark of OSI Pharmaceutical LLC, an affiliate of AstellasPharma US, and Genentech Inc. All other trademarks are the property of their respective owners.
