The gist: Cyramza, a drug recently approved for treating certain lung cancer patients, does not improve a standard treatment for stage IV non-small cell lung cancer (NSCLC). In a clinical trial, Cyramza was given to patients along with the drug pemetrexed (Alimta) and platinum chemotherapy. Some patients received only Alimta and platinum chemotherapy. None of the patients had yet been treated with chemotherapy. The researchers found that there was no significant difference between the two groups in terms of the amount of time that passed without their cancers worsening.
“In a study of patients with nonsquamous non–small cell lung cancer (NSCLC), the addition of ramucirumab (Cyramza) to pemetrexed (Alimta) and platinum chemotherapy did not significantly improve progression-free survival, according to a study by Doebele et al in Cancer. However, the investigators did suggest a possible clinical benefit of adding ramucirumab to established pemetrexed/platinum chemotherapy in patients with stage IV nonsquamous NSCLC not previously treated with chemotherapy.
“Studies have shown that patients with nonsquamous NSCLC who are treated with a combination of the platinum-containing agents pemetrexed and cisplatin have an overall survival of just 9 to 11 months. More recent studies in NSCLC have focused on the addition of targeted biologic agents, such as bevacizumab (Avastin), to platinum-containing chemotherapy to improve clinical outcomes. Bevacizumab, a humanized monoclonal antibody against the vascular endothelial growth factor ligand, is currently the only antiangiogenic agent approved for nonsquamous NSCLC. A correlation between VEGF receptor 2 (VEGFR2) expression and tumor microvessel density has been associated with a poor prognosis and lower relapse-free survival.
“With that in mind, Doebele and colleagues conducted a phase II study of the addition of ramucirumab to pemetrexed and platinum chemotherapy. Ramucirumab, a fully human immunoglobulin G1 monoclonal antibody, specifically binds to the extracellular domain of VEGFR2 with high affinity. The investigators wanted to determine whether the addition of ramucirumab to a standard first-line platinum-based combination chemotherapy regimen would result in prolonged progression-free survival….
“The results of this study indicate the addition of ramucirumab did not significantly prolong progression-free survival in patients with nonsquamous NSCLC. In addition, the overall response rate was not significantly improved for patients receiving ramucirumab vs those receiving only pemetrexed and platinum-based therapy. However, the investigators did suggest a possible clinical benefit of adding ramucirumab to established pemetrexed/platinum chemotherapy for the first-line treatment of nonsquamous NSCLC.”
The gist: Scientists have found that measuring a patient’s levels of a protein called thymidylate synthase (TS) could predict how well different kinds of chemotherapy might work for treating non-small cell lung cancer (NSCLC). Specifically, patients with low-levels of TS benefitted more from treatment with cisplatin plus pemetrexed than with cisplatin plus gemcitabine.
“A new phase II study suggests that expression of the enzyme thymidylate synthase (TS) can be used as a predictive marker for patients with non–small-cell lung cancer undergoing chemotherapy. Benefits of cisplatin plus pemetrexed over cisplatin plus gemcitabine were more pronounced in TS-negative patients than in TS-positive patients.
“ ‘Thymidylate synthase,’ said Myung-Ju Ahn, MD, of Sungkyunkwan University School of Medicine in Seoul, in a press release, ‘is targeted by pemetrexed, which is the most widely used chemotherapeutic regimen in the treatment of non-squamous NSCLC.’ Previous work has shown that the cisplatin/pemetrexed combination is superior to cisplatin/gemcitabine in non-squamous NSCLC, but levels of TS could predict the level of response.
“In this study, 315 non-squamous NSCLC patients were first stratified as either TS-positive (more than 10% of tumor cells express TS) or TS-negative, and then randomized to cisplatin plus either pemetrexed or gemcitabine. Results were presented at the European Society of Medical Oncology (ESMO) 2014 Congress in Madrid.
“The objective response rate in the cisplatin/pemetrexed patients who were TS-negative was 47%, compared with 21.1% in the cisplatin/gemcitabine group. In the TS-positive patients, meanwhile, the objective response rates were 40.3% for cisplatin/pemetrexed patients and 39.2% for cisplatin/gemcitabine patients (P = .008).”
Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to test a new treatment for women with advanced, recurrent cervical cancer. The treatment combines the drugs pemetrexed and cisplatin. The results were promising: the new treatment appeared to be safe and effective. More research needs to be done to determine just how effective it is. Also, scientists are interested in testing whether it is even more effective when combined with the targeted drug bevacizumab (Avastin).
“The combination of pemetrexed and cisplatin appeared safe and effective in women with advanced, persistent or recurrent carcinoma of the cervix, according to results of a phase 2 trial.
“ ‘This combination should be further developed in the treatment of cervical cancer,’ David Scott Miller, MD, professor of obstetrics and gynecology at UT Southwestern Medical Center, and colleagues wrote. ‘Given that it may be less toxic than and as active as cisplatin plus paclitaxel, and that it can be combined with bevacizumab (Avastin, Genentech), comparison of cisplatin–pemetrexed plus bevacizumab with cisplatin–paclitaxel plus bevacizumab would be appropriate.’ ”
The gist: A long-term study investigated the effects of new lung cancer treatments over time. They found that survival has improved for people with advanced non-small cell lung cancer (NSCLC) as new, better chemotherapy and targeted therapy treatments have been developed. The researchers also noted that survival has improved for patients who receive chemotherapy and specifically additional (“second-line”) treatment after their initial treatment.
“A 10-year population-based study shows that increased availability of better systemic chemo- and targeted-therapies for patients with advanced non-small cell lung cancer (NSCLC) coincides with increased usage of these therapies. This in turn leads to a significant increase in overall survival.
“Researchers from the British Columbia Cancer Agency, Vancouver, Canada, performed a retrospective chart review of all patients referred to the agency with advanced stage (IIIB or IV) lung cancer and grouped the patients into 4 one-year time frame cohorts; one termed ‘baseline’ and three other groups that each started 6-months after a new second-line agent (docetaxel, erlotinib and pemetrexed) was made commercially available and put into practice. In British Columbia, Canada, the implementation of the second-line agents docetaxel, erlotinib and pemetrexed occurred in December 2000, October 2005 and June 2007, respectively. Cohort 1 (January to December 1998) with 555 patients was the baseline and cohort 2 (May 2001-April 2002) had 613 patients, cohort 3 (March 2006-February 2007) had 688 patients and Cohort 4 (November 2007-Ocotober 2008) had 750 patients.
“The results published in the August Issue of the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer, show that the usage of second-line therapy increased significantly over time. At baseline only 21% of the patients received second-line therapy but in Cohorts 2 and 3 this increased to 27% and 37% respectively, and by Cohort 4 more than half, 55%, received second-line therapy. The most common agent in Cohort 1 was docetaxel (48%) but by Cohort 4 erlotinib (EGFR TKIs) and pemetrexed were used 50% and 26% of the time. The research also found that the proportion of patients who received at least first-line systemic chemotherapy also increased over the four time points from 16% in Cohort 1 to 23%, 34% and 33% for Cohorts 2-4, respectively.”
“Helix BioPharma Corp. (frankfurt:HBP), a biopharmaceutical company developing innovative drug candidates for the prevention and treatment of cancer, today announced that it has received approval from the U.S. Food and Drug Administration (“FDA”), to initiate a Phase I clinical trial with L-DOS47.
“The study is entitled “A Phase I, Open Label, Dose Escalation Study of Immunoconjugate L-DOS47 in Combination with Standard Doublet Therapy of Pemetrexed/Carboplatin in Patients with Stage IV (TNM M1a and M1b) Recurrent or Metastatic Non-Squamous Non-Small Cell Lung Cancer”.”
Editor’s note: Clinical trials can be a way for some lung cancer patients to access certain treatments they would not otherwise be able to have. Learn more.
“Updated data from the phase III AVAPERL trial hint that there might be an overall survival (OS) benefit of using bevacizumab in combination with pemetrexed as maintenance therapy in patients with advanced nonsmall cell lung cancer (NSCLC).
“ ‘The AVAPERL study was not powered to detect differences in OS between treatment arms’, Fabrice Barlesi, of Aix Marseille University in France, and colleagues observe in the Annals of Oncology.
“ ‘The analysis revealed, however, that OS was numerically increased by nearly 4 months in patients treated with maintenance bevacizumab-pemetrexed as compared with bevacizumab alone’, the international team of researchers reports.”
Editor’s Note: Maintenance therapy is “treatment that is given to help keep cancer from coming back after it has disappeared following the initial therapy. It may include treatment with drugs, vaccines, or antibodies that kill cancer cells, and it may be given for a long time,” according to the National Cancer Institute. Patients in this study were found to have longer survival times when taking a combination of the drugs bevacizumab and pemetrexed as a maintenance therapy than when taking bevacizumab alone.
The ALK inhibitor crizotinib (Xalkori) has shown effectiveness in patients with non-small cell lung cancer (NSCLC) who have changes in the ALK gene that make the gene overactive (so-called ‘ALK-positive’ patients). A recent clinical trial compared Xalkori to chemotherapy as a second-line treatment in these patients. Over 300 patients with ALK-positive advanced NSCLC who had undergone one previous round of chemotherapy were treated either with Xalkori or one of the chemotherapy drugs pemetrexed (Alimta) or docetaxel (Taxotere). Tumors shrank in 65% of Xalkori-treated patients, compared to 20% of those receiving chemotherapy. The Xalkori-treated patients also went longer without their cancer worsening, experienced fewer symptoms, and reported higher quality of life.
The U.S Food and Drug Administration (FDA) has granted regular approval to the drug crizotinib (Xalkori) for the treatment of advanced non-small cell lung cancer (NSCLC) in patients who have mutations in the ALK gene. Xalkori received accelerated approval for this application in August 2011. Regular approval was awarded based on the results of a study examining patients with advanced NSCLC whose cancer had progressed despite first-line chemotherapy. Patients treated with Xalkori went an average of 7.7 months without further cancer worsening, compared to 3.0 months in those receiving the chemotherapy agents pemetrexed (Alimta) or docetaxel (Taxotere). Tumors shrank in 65% of the Xalkori-treated patients, compared to 20% with Alimta or Taxotere. However, overall survival did not differ between the Xalkori group and the chemotherapy group.
The recent PointBreak clinical trial compared two treatment regimens for non-squamous non-small cell lung cancer (NSCLC). Previously untreated patients with advanced non-squamous NSCLC received initial treatment with carboplatin (Paraplatin), bevacizumab (Avastin), and either pemetrexed (Alimta) or paclitaxel (Taxol/Abraxane). The Alimta-treated group was then given maintenance treatment with Alimta and Avastin, while the other patients received Avastin only. Alimta treatment was associated with slightly longer times until the cancer progressed again (average 6.0 months, compared to 5.6 in the Alimta-free regimen). However, overall survival did not differ between the groups. The two regimens differed in what specific side effect were most common, but had similar overall toxicities and were generally tolerable.