“Data from two separate phase 3 studies to be presented at the ESMO 2017 Congress in Madrid, show alectinib’s particular central nervous system (CNS) activity in patients with advanced non-small cell lung cancer involving a mutation of the anaplastic lymphoma kinase gene (ALK-positive NSCLC).
Findings from the ALUR trial (1), as well as a secondary analysis of the ALEX trial (2) show alectinib can significantly decrease CNS progression of NSCLC, both in the first-line as well as the second-line treatment setting.
” ‘Patients with NSCLC have a high risk of CNS and brain metastases,’ commented Prof. Fiona Blackhall, from the University of Manchester and The Christie Hospital, UK.”
“A slightly different immunotherapy has shown benefit in the second-line treatment of non–small cell lung cancer (NSCLC).
“New data are the first to show that the programmed cell death ligand 1 (PD-L1) atezolizumab (Tecentriq, Genentech/Roche) outperforms chemotherapy in this setting. Hence, it looks set to soon join the two PD inhibitors nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck & Co) that are already approved for second-line use in NSCLC.”
“The PD-1 inhibitors pembrolizumab (Keytruda) and nivolumab (Opdivo) should be considered for all patients with advanced non–small cell lung cancer (NSCLC), especially in the second-line setting, said Roman Perez-Soler, MD, in an interview at the 10th Annual New York Lung Cancer Symposium.
“ ‘These drugs have been a gift for thoracic oncologists,’ said Perez-Soler, chairman of the Department of Oncology and chief of the Division of Medical Oncology at Montefiore Medical Center, Albert Einstein College of Medicine of Yeshiva University. ‘Because of these drugs our patients are going to live significantly longer. Our tool bag is now much more interesting. We used to have just a hammer and a screwdriver, now we have all sorts of tools.’ “
The gist: Stage IV non-small cell lung cancer (NSCLC) patients whose cancer worsened during platinum-based chemotherapy might benefit from treatment with the drug erlotinib and stereotactic body radiation (SBRT) therapy.
“Treatment with stereotactic body radiation therapy and erlotinib appeared highly effective in patients with metastatic stage IV non–small cell lung cancer who progressed on prior platinum-based chemotherapy, according to results of a single-arm phase 2 study.
“Patients with stage IV NSCLC who progress on first-line chemotherapy historically demonstrate poor survival outcomes, and they typically fail in original sites of gross disease, according to background information provided by researchers.
“Puneeth Iyengar, MD, PhD, assistant professor of radiation oncology at UT Southwestern Medical Center, and colleagues hypothesized that stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse.
“Iyengar and colleagues evaluated PFS, OS and other outcomes among 24 patients (median age, 67 years) who underwent second- or later-line treatment with SBRT plus erlotinib (Tarceva; Genentech, Astellas).”
“Amrubicin failed to improve survival over topotecan as second-line therapy for patients with sensitive small-cell lung cancer (SCLC), according to results of a new randomized phase III trial. There was, however, a small overall survival benefit seen in patients with refractory disease.
“ ‘SCLC is the most aggressive type of lung cancer,’ wrote researchers led by Joachim von Pawel, MD, of Asklepios Fachkliniken München-Gauting in Germany. ‘Despite encouraging phase II results for many targeted therapies and newer chemotherapeutic agents, current large phase III trials have failed to show improvement compared with standard of care.’ Currently, topotecan is the only approved drug for second-line therapy in SCLC patients sensitive to initial treatment; earlier work suggested the third-generation anthracycline and topoisomerase II inhibitor amrubicin could have strong activity in these patients.
“The new study included 637 patients with refractory or sensitive SCLC, assigned 2:1 to amrubicin or topotecan. The median overall survival was 7.5 months with amrubicin and 7.8 months with topotecan, for a hazard ratio of 0.880 (95% CI, 0.733-1.057; P = .170).”
Editor’s note: This article covers the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to test the effectiveness of adding a drug called ramucirumab (aka Cyramza) to treatment with the chemotherapy drug docetaxel. The patients who participated all had non-small cell lung cancer (NSCLC) that had worsened during platinum-based chemotherapy. The researchers found that ramucirumab provided patients with a small but significant improvement in survival time.
“In the phase III REVEL trial reported in The Lancet, Garon et al found that the addition of the antiangiogenic VEGFR-2 inhibitor ramucirumab (Cyramza) to docetaxel produced a statistically significant improvement in overall survival as second-line treatment in patients with stage IV non–small cell lung cancer (NSCLC) after progression on platinum-based therapy…
“In this double-blind trial, 1,253 patients with squamous or nonsquamous stage IV NSCLC from academic medical centers and community clinics in 26 countries on six continents were randomly assigned between December 2010 and January 2013 to receive docetaxel at 75 mg/m² and either ramucirumab at 10 mg/kg (n = 628) or placebo (n = 625) on day 1 of 21-day cycles until disease progression, unacceptable toxicity, withdrawal, or death. Patients had to have progressed during or after a single platinum-based chemotherapy regimen, with or without bevacizumab (Avastin) or maintenance therapy.
“Randomization was stratified by sex, region, performance status, and previous maintenance therapy. The primary endpoint was overall survival in the intent-to-treat population.”
“Cyramza™ (ramucirumab, IMC-1121B; Eli Lilly) is a human IgG1 monoclonal antibody directed against the extracellular domain of VEGFR-2. It was recently approved by the Food and Drug Administration (FDA) for advanced gastric cancer or gastroesophageal junction adenocarcinoma. On February 19, 2014, Lilly announced via press release that the REVEL trial was positive for both overall survival (OS) and progression-free survival (PFS) benefit. Results from the randomized, double-blind, placebo-controlled Phase III REVEL trial (NCT01168973) were reported at the 2014 annual meeting of the American Society of Clinical Oncology (ASCO). The trial evaluated docetaxel with or without Cyramza in squamous or non-squamous Stage IV non-small cell lung cancer (NSCLC) patients following disease progression after one prior platinum-based therapy.”
Editor’s note: A new targeted drug called Cyramza (aka ramucirumab) shows promise as a potential treatment for people with advanced non-small cell lung cancer (NSCLC). In a clinical trial, scientists tested the drug on volunteer patients with stage IV NSCLC. Compared to standard chemotherapy alone, patients who were treated with chemo plus Cyramza lived longer and had more time pass before their cancer worsened.
Update 6/9/14: According to Dr. Jack West of GRACE, the benefit of Cyramza is very minimal in the above-mentioned clinical trial, and is therefore not so promising.
“Positive results from four clinical trials of investigational targeted drugs for advanced ovarian, lung, and thyroid cancers, and chronic lymphocytic leukemia were highlighted today at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO). Findings from the mid- and late-stage trials suggest new ways to slow disease progression and improve survival for patients who experience relapses or resistance to available treatments…
“Second-line treatment with ramucirumab plus standard docetaxel extends survival for patients with advanced non-small cell lung cancer: This phase III clinical trial marks the first time in a decade that a survival benefit has been achieved in second-line therapy for patients with advanced non-small cell lung cancer – findings that could impact the care of 60,000 patients each year in the United States.”
Editor’s note: Learn more about targeted therapy drugs for lung cancer.
“There are conflicting data on whether epidermal growth factor receptor (EGFR) inhibitor therapy is beneficial in second-line treatment of lung cancer patients with unknown or wild-type EGFR status. In a phase III trial (PROSE) reported in The Lancet Oncology, Gregorc et al assessed the predictive value of a proteomic signature serum protein test for likely outcome of EGFR inhibitor therapy in non–small cell lung cancer (NSCLC) patients receiving second-line therapy with the EGFR inhibitor erlotinib (Tarceva) vs chemotherapy. They found that the test was predictive of differential survival benefit for erlotinib vs chemotherapy, with patients classified by the test as likely to have poor outcome on EGFR inhibitor therapy having better outcome on chemotherapy.”
“Overall survival was significantly better with chemotherapy among patients with a proteomic classification of poor, whereas there was no difference between chemotherapy and erlotinib in patients with a classification of good.”