Ceritinib Provides Longer Progression-Free Survival Than Chemotherapy in Phase III Trial of ALK Rearranged Lung Cancer Treatment

Excerpt:

“Ceritinib provides longer progression-free survival than chemotherapy in crizotinib-pre-treated patients with non-small-cell lung cancer harbouring an ALK rearrangement, according to results of the phase III ASCEND-5 study presented at the ESMO 2016 Congress in Copenhagen.

” ‘Patients with non-small cell lung cancer (NSCLC) should receive front line therapy with the anaplastic lymphoma kinase (ALK) inhibitor crizotinib,’ said lead author Professor Giorgio Scagliotti, head of the Department of Oncology, University of Turin, Italy. ‘Most patients develop resistance to crizotinib and currently second line treatment is represented by chemotherapy alone.’ ”

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Lung Cancer Highlights from ASCO 2016


This year, the Annual Meeting of the American Society of Clinical Oncology (ASCO) did not produce any truly groundbreaking revelations about new treatments for lung cancer. However, researchers did report quite a few positive findings, and some disappointing ones. I have summarized some of the more prominent presentations below. Continue reading…


Zykadia Shows High Response Rate Against ALK-Rearranged NSCLC in Clinical Trial

Excerpt:

“Updated results of the phase I ASCEND-1 trial, reported by Kim et al in The Lancet Oncology, indicate that the ALK inhibitor ceritinib (Zykadia) produced high response rates in advanced ALK-rearranged non–small cell lung cancer (NSCLC), including intracranial disease, in both patients with and without prior ALK inhibitor treatment.

“In the open-label trial, 246 patients enrolled from 20 sites in 11 countries in Europe, North America, and Asia-Pacific between January 2011 and July 2013 received oral ceritinib at 750 mg/d. Patients had ALK-rearranged locally advanced or metastatic disease that had progressed despite standard therapy or for which there was no effective standard therapy. A total of 83 patients had received no prior ALK inhibitor treatment, and 163 had received crizotinib (Xalkori), with 5 also receiving alectinib (Alecensa) after crizotinib. In these two groups, 53% and 54% of patients were female, 58% and 66% were white, and 42% and 29% were Asian.”

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Alectinib Shows Response in Crizotinib-Refractory NSCLC

“The ALK inhibitor alectinib was highly active and well-tolerated in patients with ALK-rearranged, crizotinib-refractory, advanced non–small-cell lung cancer (NSCLC), according to results of a phase II trial.

“In this trial, 138 patients with crizotinib-refractory ALK-positive NSCLC were treated with alectinib; 122 of these patients were evaluable for response, and 61% had central nervous system (CNS) metastases at baseline. The results were published in the Journal of Clinical Oncology.

“ ‘Almost all patients invariably experience progression on crizotinib, and approximately 40% of the patients with ALK-rearranged NSCLC develop CNS metastases as an initial site of progression,’ wrote study authors led by Sai-Hong Ignatius Ou, MD, PhD, of the Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine in Orange, California. Alectinib is approximately five times as potent an ALK inhibitor as crizotinib, and can inhibit most of the acquired ALK resistance mutations to crizotinib.”


Prognostic Factors Identified in Patients With ALK‑Rearranged NSCLC and Brain Metastasis

“In a study reported in the Journal of Clinical Oncology, Johung and colleagues identified factors that distinguished survival rates among patients with ALK-rearranged non–small cell lung cancer (NSCLC) and brain metastasis.

“The study included 90 patients from six institutions. Of them, 84 patients had received radiotherapy to the brain, consisting of stereotactic radiosurgery or whole-brain radiotherapy, and 86 patients had received tyrosine kinase inhibitor therapy (crizotinib [Xalkori] in 84 and a second-generation tyrosine kinase inhibitor in 41).”


Pfizer's Xalkori Shows First-Line Benefit in ALK-Positive NSCLC

The gist: The drug Xalkori (aka crizotinib) has shown promise for treating people with a certain type of non-small cell lung cancer (NSCLC) who have not yet taken any other treatment. A clinical trial tested Xalkori in untreated NSCLC patients whose tumors had mutations of the ALK gene (“ALK-positive”). People who took Xalkori in the trial had almost 4 more months before their cancer worsened than people who took only chemotherapy.

“Pfizer’s targeted cancer therapy Xalkori (crizotinib) significantly extended progression-free survival in previously-untreated patients with a particular form of non-small cell lung cancer taking part in a late-stage trial compared to chemotherapy alone.

“Data from the Phase III PROFILE 1014 study, published in The New England Journal of Medicine, showed that patients with ALK-positive advanced NSCLC given Pfizer’s kinase inhibitor had a median PFS of 10.9 months compared to 7 months for those in the chemotherapy arm. Also, the objective response rate was much higher at 74% versus 45%, the firm noted.

“On the safety side, no unexpected issues arose in the trial, with the most commonly reported adverse events observed in the Xalkori being vision disorder (71%), diarrohea (61%), nausea (56%) and oedema (49%), and with chemotherapy, nausea (59%), fatigue (38%), vomiting (36%) and decreased appetite (34%).

“ALK gene rearrangements are present in about 5% of NSCLC cancers typically occurring in younger patients who don’t smoke. By identifying and enrolling only those patients whose advanced NSCLC tumours are ALK-positive, “this trial was able to demonstrate the superiority of Xalkori over an intravenous platinum-based chemotherapy regimen that has been a standard first-line treatment for more than a decade,” said Mace Rothenberg, chief medical officer for Pfizer Oncology.”


Merck Receives FDA Breakthrough Therapy Designation for KEYTRUDA® (pembrolizumab) in Advanced Non-Small Cell Lung Cancer

The gist: The U.S. Food and Drug Administration (FDA) has granted “breakthrough therapy designation” to the drug Keytruda (aka pembrolizumab) for treating certain lung cancer patients. This designation means that review and approval will be accelerated so that the drug can more quickly reach patients in the U.S., outside of clinical trials. Keytruda is an immunotherapy drug, meaning that it boosts a patient’s own immune system to fight cancer. The breakthrough therapy designation specifically applies to patients with advanced non-small cell lung cancer (NSCLC) whose tumors have tested negative for EGFR mutation and ALK rearrangement, and whose disease worsened despite treatment with platinum-based chemotherapy.

“Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with Epidermal Growth Factor Receptor (EGFR) mutation-negative, and Anaplastic Lymphoma Kinase (ALK) rearrangement-negative non-small cell lung cancer (NSCLC) whose disease has progressed on or following platinum-based chemotherapy. This is the second Breakthrough Therapy Designation granted for KEYTRUDA.

“ ‘The FDA’s Breakthrough Therapy Designation of KEYTRUDA underscores that new treatment approaches for advanced non-small cell lung cancer continue to be needed,’ said Dr. Roger Perlmutter, president, Merck Research Laboratories. ‘Our data investigating the use of KEYTRUDA in this difficult-to-treat malignancy are very encouraging, and we look forward to working closely with the FDA to expedite our clinical program.’ ”


ASCO Endorses Lung Cancer Guidelines for Molecular Testing

Editor’s note: We previously posted another version of this story.

“The American Society of Clinical Oncology (ASCO) has endorsed a clinical practice guideline from several other professional associations aimed at guiding decisions on when to offer molecular testing for epidermal growth factor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in patients with non–small-cell lung cancer (NSCLC). Research on drugs targeting some of these mutations has exploded in recent years, and clinicians in practice may have had trouble keeping up with when exactly testing should be done in order to guide use of those new therapies.

“ ‘This guideline is incredibly important, as it increases the ability to personalize lung cancer care and improve outcomes for patients with advanced lung cancer,’ said Natasha B. Leighl, MD, co-chair of ASCO’s panel that endorsed the new guideline, in a press release. ‘It describes the current evidence and helps oncologists and pathologists understand and put molecular testing into clinical practice.’

“The guideline is a joint product of the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. It contains 37 distinct recommendations, opinions, or suggestions, focusing on when to test for EGFR and ALK mutations; it was published on October 13 online in the Journal of Clinical Oncology.

“The primary recommendation is to offer EGFR and ALK testing to all patients with lung adenocarcinoma (or mixed lung cancers with an adenocarcinoma component), regardless of characteristics such as smoking status, gender, or race. Small tumor samples of other histologies could be considered for testing, particularly if ‘clinical criteria are suggestive’—this would include younger age, and a lack of smoking history, among other factors.”


ASCO: Offer EGFR, ALK Testing to All Patients with Lung Adenocarcinoma

The gist: For certain types of cancer, oncologists might use molecular testing to help figure out a patient’s treatment options. Molecular testing can uncover certain genetic mutations that might make a tumor treat-able with certain kinds of drugs. Many patients with lung adenocarcinomas are already tested for EGFR mutations; a person with an EGFR mutation could be treated with an “EGFR inhibitor” drug, such as erlotinib (aka Tarceva). Now, a new guideline states that all patients with lung adenocarcinoma should be tested for both EGFR mutations and a mutation known as ALK rearrangement. Testing for these two mutations could show which patients could benefit from which targeted therapy drugs.

“ASCO today endorsed a joint clinical practice guideline from three other entities that addresses questions about the appropriate use of EGFR-mutation and ALK-rearrangement testing in patients with lung cancer.

“A key recommendation from the guideline — developed by the College of American Pathologists, the International Association for the Study of Lung Cancer and the Association for Molecular Pathology — states that clinicians should offer EGFR and ALK testing to all patients with lung adenocarcinoma, as well as those with mixed lung cancer with an adenocarcinoma component.

“The testing should be offered regardless of characteristics — such as smoking status, gender and race — to help determine which patients could benefit from targeted therapy with tyrosine kinase inhibitors, according to the guideline.

“ ‘This guideline is incredibly important, as it increases the ability to personalize lung cancer care and improve outcomes for patients with advanced lung cancer,’ Natasha B. Leighl, MD, MSc, medical oncologist at Princess Margaret Hospital in Toronto and co-chair of the ASCO expert panel that reviewed and endorsed the guideline, said in a press release. ‘It describes the current evidence and helps oncologists and pathologists understand and put molecular testing into clinical practice.’

“Patients with advanced-stage disease should be offered testing at the time of diagnosis, and patients with lower-stage disease should undergo testing at the time of progression or recurrence, the guideline states.”