In November of 2014, Phil Kauffman went to his primary care doctor with what he thought was a broken rib. The doctor advised him to let it heal on its own—a standard approach for such maladies.
Phil, a retired engineering consultant who lives near San Diego, California, with his wife (their two daughters are grown), went home and waited for his rib to heal, but the pain stuck around for months.
In March of 2015 his doctor ordered an X-ray, but instead of a broken rib, it revealed suspicious spots in Phil’s lung. A CT scan found five lesions characteristic of lung cancer. His rib pain was caused by pleural effusion (liquid) in his right lung, which was extracted, and an examination of that liquid confirmed a diagnosis of stage IV non-small cell lung cancer (NSCLC).
Phil remembers that during the first week after his diagnosis he was paralyzed with fear. His brother in law, a physician, helped him snap out of it, assuring him that his treatment options guaranteed a survival period of at least a few years or maybe more, and that cancer research was progressing at such a fast rate that the prospect of extending his lifetime beyond a couple of years was good. Continue reading…
“U.S. health regulators approved expanding the use of Merck & Co.’s cancer drug Keytruda to include adding it to chemotherapy to treat lung cancer, broadening the drug’s potential market though evidence for the combination’s benefit is mixed.
“Keytruda, introduced in 2014, is one of a new wave of cancer drugs designed to work by harnessing the body’s own immune system to fight tumors. The U.S. Food and Drug Administration on Wednesday approved combining it with two chemotherapy agents, pemetrexed and carboplatin, to treat patients with an advanced form of lung cancer. Eli Lilly & Co. markets pemetrexed under the brand Alimta, and carboplatin is available generically.”
“The combination of pemetrexed and gefitinib offered improved progression-free survival (PFS) over gefitinib alone in East Asian patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) and activating EGFR mutations, according to a new randomized, open-label study.
“EGFR tyrosine kinase inhibitors (TKIs) including gefitinib have been shown to improve outcomes in patients with EGFR-mutated NSCLC. ‘Given their different mechanisms of action, combination treatment with EGFR-TKIs and chemotherapy may further improve outcomes,’ wrote study authors led by James Chih-Hsin Yang, MD, PhD, of National Taiwan University Hospital in Taipei. Previous trials of such combinations have not shown clinical benefit, however, though this could have been because of antagonism between the agents used or because wild-type EGFR patients were included.”
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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.”
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 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.
Personalized cancer medicine uses genetic testing of patients’ tumors to guide individually tailored treatment decisions. Such tests can determine which chemotherapies would likely be most effective and whether the patient may benefit from novel drugs targeting specific mutations. One example is the case of Elizabeth Lacasia, who has advanced bronchioalveolar carcinoma, a type of non-small cell lung cancer (NSCLC). Testing revealed that she does not have any of the mutations targeted by the new drugs. Based on her test results, she was treated with a combination of Tarceva (erlotinib) and Alimta (pemetrexed) following an alternating schedule that has been proven effective for people with her cancer type. Her cancer has been in remission for 2 years.