“Small cell lung cancer (SCLC) is an aggressive disease that is difficult to treat and is frequently only diagnosed when it has spread to other parts of the body (metastasised). Five-year survival rates in SCLC, which accounts for about 14% of all lung cancers, are very low, at only six percent. But today US researchers will present two novel findings with important implications for treatment at the 2015 European Cancer Congress.
“Dr M. Catherine Pietanza, MD, an Assistant Attending Physician at the Memorial Sloan Kettering Cancer Center, New York, USA, will report on results from a phase I trial of a novel agent, rovalpituzumab tesirine (Rova-T, or S16LD6.5), in 79 patients with SCLC who had progressed after first line (given when the disease is newly diagnosed) or second line therapy (given when the disease progresses or recurs).
” ‘While other cancers have multiple treatment options, there is only one agent approved in SCLC, and none available in the third line setting; the outlook for these patients is dismal,’ she will say. Third line therapy is given after first and second line treatments have failed to halt the progression of disease.”
“ ‘The primary underpinning of the trial comes from genetic characterization of various cancer types, which has become increasingly common place but is not yet routine,’ Keith T. Flaherty, MD, an oncologist at Massachusetts General Hospital, associate professor at Harvard Medical School andECOG-ACRIN chair of the NCI-MATCH trial, told HemOnc Today. ‘When looking at cancers as defined by their site of origin, there are threads of continuity across those cancer types. Within a cancer type, there also is heterogeneity, and understanding what this patchwork looks like was really the main motivator for setting up a trial like this.’ “
“Targeted treatments for cancer have been extending and saving lives for more than 15 years—precision medicine isn’t a new idea in oncology. Now drugs pioneered on select, specific cancers are, one by one, finding new applications.
“The first wave of targeted drug approvals were for cancers associated with specific mutations. Herceptin (traztuzumab) led the way, approved in 1998. It’s a monoclonal antibody deployed against the HER2/neu receptor that is overabundant in some aggressive and early-onset breast cancers. Robert Bazell’s excellent book Her 2 tells the tale.
“In 2001 came the blockbuster Gleevec (imatinib), a small molecule tyrosine kinase inhibitor that intercepts signals to divide. Erin Zammett’s My So-Called Normal Life with Cancer relates that story. A very young editor at Glamour magazine when a routine check-up revealed chronic myelogenous leukemia, Erin’s recovery was one of the first of thousands thanks to this now famous drug.”
“She had come to see me as a second opinion; diagnosed with uterine serous cancer, one of the more aggressive types of uterine cancers. At surgery they found that it had metastasized to her nodes—stage III disease. The surgery was successful, though, and she had been treated with adjuvant chemotherapy with the hope it was curative. Two years later, she developed abdominal pain. A work-up showed that her CA-125 was elevated, which prompted a scan, and a diagnosis of hepatic metastases. Her doctors recommended repeat treatment with chemotherapy—carboplatin and paclitaxel. ‘It didn’t work the first time, so I am not sure doing it all over again makes sense.’ “
“A new kind of cancer study supports the idea that traditional treatment can be turned on its head, with patients given targeted therapy based not on where their tumors started but on their own genetic mutations.
“Researchers used a targeted melanoma drug to treat patients with a range of cancers, from lung cancer to brain cancer, who weren’t being helped by traditional chemotherapy any more. Even though they had many different types of tumors, they all had one thing in common — a genetic mutation called BRAFV600.
“It’s a mutation familiar to doctors who treat melanoma, the deadliest form of skin cancer. It’s seen in about half of melanoma cases. A pill called vemurafenib, sold under the brand name Zelboraf, specifically targets the mutation. It helps about half of patients with melanoma who have the mutation.
“The same mutation is sometimes seen in colon cancer, lung cancer, thyroid cancer, brain tumors and some blood cancers.”
“While targeting HER2 mutations is mainly associated with breast cancer, there could be therapeutic potential with anti-HER2 agents in non-small cell lung cancer (NSCLC). At this year’s International Lung Cancer Congress, Corey Langer, MD, discussed the potential for afatinib and neratinib—dual inhibitors of EGFR and HER2—in NSCLC, as well as the need for additional research, in order to truly comprehend HER2 targeted therapy in this particular setting.
“HER2 mutations occur in about 2% to 4% of patients with NSCLC, and for the most part, they are mutually exclusive with other molecular drivers (eg, EGFR, KRAS), according to Langer, director of Thoracic Oncology at the Abramson Cancer Center of the University of Pennsylvania. “Similar to EGFR and ALK, the HER2 mutations are more common in women, never-smokers, and adenocarcinoma histology,” Langer added.
“Regarding use of afatinib in these patients, Langer said, ‘There are limited but encouraging data in patients with HER2-mutant NSCLC treated with either afatinib or afatinib plus paclitaxel.’ “
“HER2 and hormone-receptor status should form the basis for biomarker testing in metastatic breast cancer, according to a new clinical practice guideline from the American Society of Clinical Oncology (ASCO).
“All patients with accessible metastases should have biopsies to determine disease status. Retesting of HER2, estrogen receptor, and progesterone status should be offered, although data are insufficient to know whether a change in therapy based on the markers’ status will affect outcomes.
“In the case of discordant findings from biopsies of primary tumors and metastases, the marker status of the metastasis should take precedence with respect to treatment decisions, Catherine Van Poznak, MD, of the University of Michigan in Ann Arbor, and colleagues advised in a statement published online in the Journal of Clinical Oncology. Tests for carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3 and CA 27-29 may be used adjunctively but not by themselves.”
“The combination of lapatinib (Tykerb) and trastuzumab (Herceptin) is active and well-tolerated when given to patients with human epidermal growth factor receptor 2-positive (HER2) metastatic breast cancer (MBC) who have received up to two lines of therapy for advanced disease, a nonrandomized phase II study now shows.
“What’s more, early metabolic imaging by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) appears to provide the key to selecting patients who can be treated with targeted regimens and spared the toxicity of chemotherapy, Nancy U. Lin, MD, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, Ma., and colleagues report online in the Journal of Clinical Oncology.
” ‘Because the number of treatment options and their cost for patients with HER2-positive breast cancer continues to increase, a key question is how best to tailor therapies to individual patients,’ said Lin. ‘In the metastatic setting, predictive tests for clinical benefit could spare patients unnecessary toxicity and cost from ineffective therapies and maximize the likelihood of meaningful improvements from treatment. In the early-stage setting, predictive tests may reduce both under- and overtreatment.’ “
“Iressa (gefitinib) has been approved by the U.S. Food and Drug Administration to treat patients with metastatic non-small-cell lung cancer (NSCLC) with a specific genetic mutation (epidermal growth factor receptor [EGFR]). A just-approved companion diagnostic test can identify patients who could benefit from this new use.
“Iressa is a kinase inhibitor, a class of drugs designed to block proteins that spur development of cancer cells. The therascreen EGFR RGQ PCR Kit is a newly approved diagnostic that can help doctors detect patients with the genetic mutation who are candidates for treatment with Iressa.
“Iressa was evaluated for this use in clinical trials involving 106 people with previously untreated EGFR mutation-positive metastatic NSCLC. Tumors shrank in about 50 percent of people treated with Iressa 250 mg once daily. This effect lasted an average of six months, the FDA said. Severe side effects of Iressa may include interstitial lung disease, liver damage, gastrointestinal perforation, severe diarrhea, and ocular disorders. More common side effects are diarrhea and skin reactions.”