In this slide show we highlight some of the top news on lung cancer in 2017, including FDA approvals, a new standard of care for ALK-positive lung cancer, increased risk with vitamin B supplements, and more.
Gut Bacteria Predict Responses, Survival Time to PD-1 Cancer Immunotherapy: According to two published studies, efficacy of PD-1 immune checkpoint blockade immunotherapy in cancers such as lung and melanoma are affected by the gut microbiome. Researchers of the first study noted that the gut bacteria diversity and composition indeed predicted PD-1 inhibitor responses among patients with melanoma. Longer progression-free survival, increased responses, and higher concentrations of T-cells were noted in patients with more Ruminococcaceae-order and fewer Bacteroidales-order species. The second study reported that patients with lung and other cancers experienced faster relapse rates during treatment with immunotherapy compared with those who had taken antibiotics within 2 months before starting PD-1/PD-L1 blockade immunotherapy, or within a month of starting therapy. Patients who responded had more Akkermansia muciniphila, which inhabits the gut’s mucus lining, and Ruminococcus bacteria in their guts than did non-responders. Read more. Image © Anatomy Insider/Shutterstock.com
Bevacizumab Does Not Improve Outcomes With Chemotherapy in Early NSCLC: The results of an open-label, randomized phase III study report that adding bevacizumab to adjuvant chemotherapy did not improve survival outcomes in patients with surgically resected early-stage non–small-cell lung cancer (NSCLC). At the sixth planned interim analysis, the median noted follow-up for surviving patients was 50.3 months; the median overall survival (OS) of the bevacizumab arm was 85.8 months. The chemotherapy-alone arm had not reached an OS rate. In the bevacizumab group, the median disease-free survival was 40.6 months versus 42.9 months in the chemotherapy-alone arm yielding a hazard ration (HR) of 0.99 (95% CI, 0.86–1.15; P = .95). Researchers note that subgroup analyses did not show significant differences between treatments. Read more. Image © Brian A Jackson/Shutterstock.com
Survival in Metastatic Lung Cancer Improved With SBRT Before Maintenance Chemo: According to the results of a phase II study presented at the 2017 American Society for Radiation Oncology (ASTRO), patients with limited metastatic non–small-cell lung cancer (NSCLC) who underwent stereotactic body radiation therapy (SBRT) prior to starting maintenance chemotherapy experienced a significantly improved progression-free survival (PFS). The small study of patients with stage IV NSCLC limited to six or fewer sites were randomized to maintenance chemo with or without consolidative SBRT to all sites of disease. At 9.6 months, it was noted that the patients in the SBRT arm experienced a PFS of more than double compared with the patients undergoing maintenance chemotherapy alone (9.7 vs 3.5 months; hazard ratio [HR], 0.304; 95% CI, 0.113–0.815; P = .01). Read more. Image © adriaticfoto/Shutterstock.com
Vitamin B Supplementation Linked With Increased Lung Cancer Risk in Men: The results of a recent study report that supplementation with individual B vitamins (not multivitamins) was associated with an increased risk for developing lung cancer in men. At a mean follow-up of 6 years, the VITAL trial reported 808 primary invasive lung cancers of the 77,118 person cohort. Men who were former users of vitamin B6 individual supplements experienced a higher risk of lung cancer versus nonusers; the multivariate hazard ratio (HR) was noted to be 1.84 (95% CI, 1.01–3.36). Interestingly, this elevation was not seen in women or with multivitamin supplementation. In those men (not women) who were former B12 supplement users, the HR for lung cancer was 2.42 (95% CI, 1.49–3.95) compared with nonusers. Men who smoked at baseline experienced a higher risk of lung cancer with both types of vitamin B supplementation. Read more. Image © haryigit/Shutterstock.com
FDA Approves First Biosimilar for Cancer Treatment: The US Food and Drug Administration (FDA) has approved the first biosimilar drug for cancer treatment in the United States. Mvasi (bevacizumab-awwb, Amgen) was approved based on the findings of data that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Mvasi is biosimilar to Avastin (bevacizumab, Genentech) for the treatment of cancers including colorectal, lung, brain, kidney, and cervical cancers. Although Mvasi has been approved as a biosimilar to Avastin, the FDA reports that it is not an interchangeable product. For patients with nonsquamous non–small cell lung cancer, Mvasi is approved for use in combination with carboplatin and paclitaxel for the first-line treatment of unresectable, locally advanced, recurrent, or metastatic disease. Read more. Image © Hurst Photo/Shutterstock.com
Cancer Risk Elevated Among Holocaust Survivors: Findings of a recent study report that Holocaust survivors have a small but consistent increase in the risk of developing cancer, especially colorectal and lung cancers. The study followed 152,622 Holocaust survivors over a span of 45 years, mainly analyzing cancer rates amongst individuals who were entitled to compensation for suffering persecution during the war and individuals who were denied compensation. Researchers found that there were cancer diagnoses in 22% of those who were granted compensation for suffering persecution during the war vs. 16% of those who were denied compensation. There was a noted 6% increase in all type cancers, a 12% increase in colorectal cancers, and a 37% increase in lung cancers; no increases in breast or gynecologic cancers were noted. Researchers theorize that nutritional mineral deficits and smoking may have contributed to the development of colorectal and lung cancers respectively. Read more. Image © praszkiewicz/Shutterstock.com
First-Line Nivolumab in Advanced Lung Cancer Fails to Improve Outcomes: According to the results of an open-label phase III clinical trial, nivolumab did not extend progression-free survival over chemotherapy in the first-line setting in patients with programmed cell death ligand 1 (PD-L1)-positive advanced non-small cell lung cancer (NSCLC). The study compared nivolumab as first-line therapy in patients with PD-L1 expression levels of 5% or more, randomizing participants to receive nivolumab or platinum-based chemotherapy. Median progression-free survival at a median follow-up of 13.5 months revealed 4.2 months in the nivolumab arm compared with 5.9 months in the chemotherapy arm. Subjects who received nivolumab experienced a mean overall survival of 14.4 months versus 13.2 months in the chemotherapy arm. Researchers point out that 60% of patients in the chemotherapy arm ended up receiving nivolumab, which they note could have contributed to the long overall survival in these patients (33% chemotherapy) vs 26% nivolumab). Read more.
Tailoring Chemo to BRCA1 Levels Did Not Improve Survival in Early Lung Cancer: According to the results of a new trial presented at the 2017 International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer, there was no increase in overall survival rates in patients with early-stage, resected, node-positive non–small-cell lung cancer (NSCLC) who were treated with customized chemotherapy based on BRCA1 expression levels. The 500 study participants were randomly assigned control group treatment with cisplatin/docetaxel or experimental treatment with cisplatin/gemcitabine (low BRCA1 expression), cisplatin/docetaxel (intermediate expression), or docetaxel alone (high expression). There was no significant difference in overall survival in the study arms, with a median 53-month follow-up overall survival rate of 69.3 months in the control group versus 82.3 months in the experimental group. Within the experimental arm, researchers noted that survival ranged from 74 months (low BRCA1) to 80.5 months (intermediate expression) to 80.2 months (high expression). Read more. Image © YAKOBCHUK VIACHESLAV/Shutterstock.com
Alectinib Touted as New Standard of Care for ALK-Positive Lung Cancer: According to the results of a new open-label, multicenter, phase III study presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, alectinib, the second-generation anaplastic lymphoma kinase (ALK) inhibitor, should now be the new standard of care for first-line treatment of ALK-positive non–small-cell lung cancer (NSCLC). Researchers report that alectinib halted cancer growth for a median of 15 months longer and patients experienced fewer severe side effects than the current standard of care, crizotinib. At 1 year, researchers noted a 53% reduced risk for disease progression versus crizotinib with a progression-free survival of 25.7 months versus 10.4 months on crizotinib. Researchers reported an 84% reduction in CNS progression in patients in the alectinib arm versus crizotinib (9.4% vs 41.4%). Additionally, those in the alectinib arm experienced less severe side effects compared with crizotinib. Read more. Photo by © ASCO/Scott Morgan 2017
Ceritinib Gets First-Line FDA Approval for ALK-Positive Lung Cancer: Based on the results of the randomized ASCEND-4 trial, the US Food and Drug Administration (FDA) has expanded the approval for ceritinib to be included as a first-line treatment in patients with metastatic, ALK-positive, non-small-cell lung cancer (NSCLC). Researchers report a median progression-free survival of 16.6 months with ceritinib versus 8.1 months in the chemotherapy arm with a hazard ratio of 0.55 (95% CI, 0.42–0.73; P < .0001). The ceritinib arm also experienced a 73% overall response rate versus 27% in the chemotherapy arm, with a median response duration of 23.9 months in the ceritinib arm versus 11.1 months with platinum/pemetrexed treatment. Intracranial disease response rates for those with measurable disease in the ceritinib arm was 57% versus 22% in the chemotherapy arm. Read more. Image © molekuul_be/Shutterstock.com
FDA Approves New First-Line Lung Cancer Treatment: Based on the results of the open-label, randomized, multicenter cohort trial, KEYNOTE-021, the US Food and Drug Administration has approval the anti–PD-1 immunotherapy pembrolizumab, in combination with pemetrexed and carboplatin for patients with untreated metastatic non-squamous non-small cell lung cancer (NSCLC). The KEYNOTE-21 trial evaluated 4 cycles of pemetrexed and carboplatin in 63 patients vs pemetrexed/carboplatin plus 200-mg pembrolizumab intravenously every 3 weeks in 60 patients until progression or unacceptable toxicity. Pemetrexed could be administered as maintenance therapy at the investigators discretion. There was in improved overall response rate and progression-free survival (PFS) rate in those who received pembrolizumab. Researchers note an overall response rate of 55% in those receiving pembrolizumab plus chemotherapy vs 29% in those who received chemotherapy alone. They go on to note a median PFS rate of 13 months in the pembrolizumab arm versus 8.9 months in the chemotherapy-alone arm. Read more.
Flu Vaccine in Lung Cancer Patients Could Increase Immunotherapy Toxicities: The results of a small study presented at the European Lung Cancer Conference in Geneva report that the seasonal influenza vaccination resulted in increased risk of immune-related adverse events (AEs) in lung cancer patients treated with PD-1/PD-L1 checkpoint inhibitors. While the vaccine proved effective in all patients, researchers noted a higher than expected frequency of immune-related AEs, which occurred in 52.2% of patients. Of the study participants, 26.1% experienced a grade 3 or 4 immune-related AE such as skin rashes, arthritis, colitis, encephalitis, hypothyroidism, pneumonitis, and neuropathy. Researchers note that this frequency is higher than expected versus that of unvaccinated patients who per literature analysis typically experience a 30%-35% immune-related AE rate. Researchers hypothesize that vaccination with the seasonal flu vaccine results in immune system activation in this population of patients. It is noted, however, that the risks of the flu may outweigh risks of vaccination. Read more. Image © DonyaHHI/Shutterstock.com
FDA Approves Brigatinib for Lung Cancer: Brigatinib was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic anaplastic lymphoma kinase (ALK)-positive non–small-cell lung cancer (NSCLC), specifically in those patients with disease progression on or who are intolerant to crizotinib. Approval comes after publication of the ALTA trial results, a two-arm, open-label trial evaluating 222 patients with documented ALK rearrangement who had progressed on crizotinib. The trial included 112 patients who received 90-mg brigatinib daily versus those receiving 180-mg once daily following a 7-day lead-in at the lower dose; median follow-up was 8 months. In the 90-mg per day group, there was a 48% overall response rate compared with 53% in the 180 mg arm; both groups experienced a 13.8-month median duration of response. Therefore, the FDA recommends a lead-in with the 90 mg dose, followed by an increase to 180 mg once daily if tolerated. Read more.
Frontline Ceritinib Doubles PFS in ALK-Rearranged Lung Cancer: Results of a new phase III study (ASCEND-4) report that ceritinib, the oral ALK inhibitor, provided patients with previously untreated ALK-rearranged non–small-cell lung cancer (NSCLC) significant improvement in progression-free survival (PFS) over platinum-based chemotherapy. All patients included in the trial had stage IIIB/IV ALK-rearranged non-squamous NSCLC and were randomized to receive ceritinib or chemotherapy. A blinded independent review committee reported a median PFS of 16.6 months with ceritinib versus 8.1 months with chemotherapy. Those with brain metastases experienced a 26.3-month PFS with ceritinib versus 8.3 months with chemotherapy. The median PFS in those with brain metastasis was not clinically significant with PFS (10.7 months in the ceritinib group vs 6.7 months in the chemotherapy group). While the overall survival data was not mature, there was a trending advantage toward those receiving ceritinib. Read more. Image © Dragon Images/Shutterstock.com
MEK Inhibitor Adds No Value in Treatment of KRAS-Mutant NSCLC: Researchers from the Dana-Farber Cancer Institute report that the addition of selumetinib to docetaxel does not provide any significant benefit over docetaxel alone for patients previously treated for advanced KRAS-mutant non-small cell lung cancer (NSCLC). The large, randomized, multi-center trial included patients who either received selumetinib plus docetaxel or placebo plus docetaxel. The median progression-free survival (PFS) and overall survival (OS) did not reveal significant differences in either group, with a median PFS of 3.9 for those randomized to the selumetinib arm and 2.8 months in the placebo arm. The study reported an OS of 8.7 months in the selumetinib arm and 7.9 months with the placebo arm. Researchers noted an objective response rate (ORR) of 20.1% in the treatment arm versus 13.7% in the placebo arm. Median duration of response was 2.9 months with the two-drug combination and 4.5 months with docetaxel alone. Read more. Image © molekuul_be/Shutterstock.com