“Immune checkpoint inhibitors have revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC). In patients progressing on first-line therapy, immunotherapy with the PD-1/PD-L1 inhibitors pembrolizumab, nivolumab, and atezolizumab has become standard second-line therapy. While these agents are associated with durable responses and long-term improvements in overall survival (OS), only a small proportion of patients respond to treatment. Relatively little is known about the factors that predispose patients to response on checkpoint inhibitors, and there is an unmet need for improved patient selection criteria.”
“The FDA has granted a priority review to a supplemental new drug application (sNDA) for the use of osimertinib (Tagrisso) as a first-line treatment for patients with non–small cell lung cancer (NSCLC) whose tumors harbor EGFR mutations (exon 19 deletions or exon 21 [L858R] substitution mutations).
“The sNDA is based on the phase III FLAURA study, in which frontline osimertinib reduced the risk of progression or death by 54% versus standard TKI therapy—erlotinib (Tarceva) or gefitinib (Iressa). In the double-blind study, the median progression-free survival (PFS) was 10.2 months (95% CI, 9.6-11.1) for standard therapy and 18.9 months (95% CI, 12.5-21.4) with osimertinib (HR, 0.46; 95% CI, 0.37-0.57; P <.0001).”
“Non-small cell lung cancer (NSCLC) patients with common epidermal growth factor (EGFR) mutations and brain metastases showed improved progression-free survival (PFS) and response from the EGFR tyrosine kinase inhibitor (TKI) afatinib compared to standard platinum doublet chemotherapy.
“More than 25% of patients with advanced NSCLC experience progression to the brain from their primary lung cancer and this number increases to 44-63% for those NSCLC tumors driven by EGFR mutations. Prognosis is poor and typically ranges for 1-5 months for those with brain metastases. EGFR TKIs are highly effective therapies for advanced NSCLC driven by EGFR mutations, especially the common mutations, exon 19 deletions and L858R point mutations. Even though there are a number of EGFR TKIs approved for first-line therapy of EGFR mutation positive NSCLC, there is a scarcity of prospective data for EGFR TKIs in patients with brain metastases.”
Update: We are deeply saddened to report that Craig passed away on March 16, 2016. It is a privilege to continue to share his story and keep his memory alive.
In 2010, Craig Blower had such a bad case of bronchitis that his doctor put him on steroids. Craig’s airways cleared up in a month or two, and he didn’t give it any more thought. Then, in late 2012, his throat began whistling slightly when he woke up. But Craig, who was 59 years old at the time, thought it was just part of getting older. “I basically ignored it,” he recalls. Continue reading…
“Osimertinib (AZD9291), the third-generation TKI, demonstrated a 71% objective response rate (ORR) in those with EGFR T790M-mutant non-small cell lung cancer (NSCLC), following resistance to frontline anti-EGFR therapy, according the findings of the phase II AURA2 trial that was presented at this year’s World Conference on Lung Cancer (WCLC).
“The ORR consisted of 2 complete responses and 139 partial responses. The stable disease rate at ≥6 weeks was 21%, for a disease control rate of 92%. After a median follow-up of 6.7 months, the median progression-free survival (PFS) was 8.6 months. The median duration of response was 7.8 months (27% maturity).”
The gist: Scientists hope that a promising drug called rociletinib could be combined with a drug called trametinib to treat people with non-small cell lung cancer (NSCLC) whose tumors have mutations in the EGFR gene. Both drugs are targeted therapy drugs. The combination might help treat people whose tumors are resistant to other targeted treatments, due to EGFR T790M mutations. The combination will be tested soon in a clinical trial with volunteer patients. Later, other clinical trials might try combining rociletinib with other drugs.
“ ‘We have seen significant activity in EGFR mutant NSCLC patients treated with rociletinib monotherapy, and so an important next step in our research is to examine rociletinib in combination with other targeted therapies that may also impact acquired resistance to EGFR inhibitors,’ said Lecia V. Sequist, MD, MPH, Massachusetts General Hospital Cancer Center and Associate Professor of Medicine at Harvard Medical School and the lead investigator for this combination study.
“ ‘As we continue to see compelling activity for rociletinib single-agent therapy at our selected dose, we look forward to exploring combination trials in both T790M-positive and T790M-negative patients,’ said Patrick J. Mahaffy, President and CEO of Clovis Oncology. ‘We believe that given the tolerability profile of rociletinib, particularly its lack of cutaneous toxicity, it may be a good candidate for combination therapy with trametinib, and other relevant targeted therapies. We intend to announce additional combination studies over the next few months.’ “
“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.”
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.”
Lopez-Rios F, Angulo B ... Lawrence HJ, de Castro DG, J Clin Pathol, Feb 5, 2013
We aimed to conduct a methods correlation study of three different assays for the detection of mutations at EGFR gene in human formalin-fixed paraffin-embedded tumour (FFPET) specimens of non-small cell lung carcinomas (NSCLC).
The invalid rates for the cobas test and Therascreen were lower than Sanger sequencing. The cobas and Therascreen assays showed a high degree of concordance, and both were more sensitive for the detection of exon 19 deletion and L858R mutations than Sanger. The cobas test was highly reproducible between the two testing sites, used the least amount of DNA input and was the only test with automated results reporting.