A New Drug Shows Promise in Small Cell and Non-Small Cell Lung Cancer

“Immunomedics, Inc., (Nasdaq:IMMU) today announced that 33% of patients with small cell lung cancer (SCLC) and 31% with non-small cell lung cancer (NSCLC) had their tumor reduced in size by 30% or more, after being treated with sacituzumab govitecan, the Company’s lead investigational antibody-drug conjugate (ADC). Including patients that reported stable disease as their best response, the ADC controls the progression of the cancer in 75% and 56% of NSCLC and SCLC patients, respectively. These patients had either failed to respond to their last lung cancer therapies or their cancer had returned or progressed.

“Dr. Francois Wilhelm, Chief Medical Officer, presented the updated results at the 15th Annual Targeted Therapies of Lung Cancer Meeting, an invitation-only meeting sponsored by The International Association for the Study of Lung Cancer (IASLC).

“Sacituzumab govitecan is a next generation ADC designed for targeted therapy of solid cancers. The agent was created by site-specifically conjugating a TROP-2-targeting antibody with a high ratio of a moderately toxic drug, SN-38, using a pH sensitive linker. TROP-2 is a receptor found on many human cancer cells, such as cancers of the breast, cervix, colon and rectum, kidney, liver, lung, ovary, pancreas, and prostate, but with only limited expression in normal human tissues. In an animal model of human pancreatic cancer, the ADC delivered up to 135-times the amount of SN-38 to the tumor than when irinotecan, the parent drug of SN-38, was given.”

Surgery for Stage I SCLC Provides Survival Benefit

The gist: A recent study found that people with stage I small cell lung cancer (SCLC) might survive longer if they have surgery to remove part of the lung affected by cancer. The study compared survival rates between patients who had surgery and patients who had other forms of treatment. Five years after treatment, 62% of the patients who had surgery were still alive, compared to 25% of the patients who did not have surgery.

“Patients with stage I limited-disease small cell lung cancer who underwent surgical resection demonstrated a significant survival advantage compared with those who received nonsurgical treatment, according to results of a retrospective study.

“Surgical resection also appeared effective in some patients with stage II or stage II limited-disease small cell lung cancer (LD-SCLC), results showed.

“ ‘Although chemotherapy and radiotherapy are recommended for patients with LD-SCLC, several series have reported favorable survival outcomes even in patients with stage II and stage III disease who underwent surgical resection,’ Tomoyoshi Takenaka, MD,of the department of thoracic oncology at National Kyushu Cancer Center in Fukuoka, Japan, and colleagues wrote.

“In the current study, Takenaka and colleagues analyzed the outcomes of 277 patients aged 38 to 89 years (median, 66 years; 81% men) treated for LD-SCLC from 1974 to 2011 at National Kyushu Cancer Center…

“ ‘Surgical resection provided a survival benefit for the patients with clinical stage I SCLC and some cases of stage II or stage III disease in this study,’ Takenaka and colleagues wrote. ‘The outcomes of treatment for SCLC have been improved beginning in the 2000s. A further prospective study is warranted to clarity the possibility of extending the indications for surgical resection to curatively treat LD-SCLC in the present situation.’ ”

FDA Names New Drug Tarextumab "Orphan Drug" for Small Cell Lung Cancer

The gist: The U.S. Food and Drug Administration (FDA) has granted “orphan drug” designation to a new drug called tarextumab for small cell lung cancer (SCLC) and pancreatic cancer. The designation will make it easier for the drug maker to successfully develop tarextumab and get it to patients in the U.S. Tarextumab has shown promise in patients in a clinical trial. It is given to patients in combination with chemotherapy.

“The US Food and Drug Administration (FDA) has granted orphan drug designation to the OncoMed agent tarextumab for the treatment of pancreatic cancer and lung cancer. Tarextumab (formerly OMP-59R5) is a fully human monoclonal antibody targeting the Notch 2/3 receptors.

“ ‘We are excited to receive two separate orphan drug designations for tarextumab for the treatment of pancreatic and small-cell lung cancer,’ said Paul J. Hastings, OncoMed’s chairman and chief executive officer, in a statement.

“Earlier this month the drug company announced final phase 1b clinical and biomarker data from the ALPINE (Antibody Therapy in First-Line Pancreatic Cancer Investigating Anti-Notch Efficacy and Safety) study, which tested tarextumab in combination with gemcitabine plus nab-paclitaxel in pancreatic cancer.

“Of the 29 patients in the trial, 21 (73%) achieved either a partial response or stable disease with the combination therapy.”

After Promising Early Results, Drug to Continue Testing in More Relapsed SCLC Patients

The gist: In a clinical trial, a new drug called PM1183 showed promise for treating people with small cell lung cancer (SCLC). Based on those results, the drug will be tested in more people in a new phase III clinical trial. PM1183 will be given to patients along with the drug doxorubicin. For comparison, some patients will only be treated with the drug topotecan. The trial will enroll patients who have SCLC that returned (relapsed) after standard treatment.

“Zeltia announces today that its pharmaceutical division PharmaMar will start a Phase III trial with PM1183 in combination with doxorubicin against topotecan in SCLC, given the activity observed in an interim analysis of an ongoing Phase Ib trial. The results of this study will be presented at a prominent international cancer meeting this year, which will be soon announced.

“Patients with small cell lung cancer (SCLC) after failure of standard chemotherapy, as well as bladder, gastric, breast, endometrial or ovarian cancer, neuroendocrine tumors and soft-tissue sarcomas were treated with the combination in a Phase I. The treatment showed efficacy across all cancer types, including several complete responses. This clinical response was remarkable in certain tumor types, particularly in SCLC, and consequently more patients with this type of tumor were enrolled. The treatment was generally well-tolerated, and these patients had marked objective tumor responses and were able to receive several cycles of treatment.

” ‘The data we have are very exciting as patients with SCLC have the worst prognosis among lung cancer patient. There have been no significant advances in 25 years in this type of lung cancer.’ says Luis Mora, Managing Director, PharmaMar.”

New Agent Causes Small Cell Lung Tumors to Shrink in Pre-Clinical Testing

The gist: Scientists are working on a potential new treatment for small cell lung cancer (SCLC) that looks promising in mice, but it has not yet been tested in patients. The drug is called THZ1. In mice, it shrank tumors significantly. It may soon be tested in patients in clinical trials.

“Small cell lung cancer – a disease for which no new drugs have been approved for many years – has shown itself vulnerable to an agent that disables part of tumor cells’ basic survival machinery, researchers at Dana-Farber Cancer Institute and the Massachusetts Institute of Technology reported.

“In a study published today in the journal Cancer Cell, the investigators found that the agent THZ1 caused human-like small cell lung tumors in mice to shrink significantly, with no apparent side effects. The compound is now being developed into a drug for testing in human patients in clinical trials.

” ‘Small cell lung cancer is a disease for which new treatments are desperately needed,’ said Kwok-Kin Wong, MD, PhD, co-senior author of the study and medical oncologist at Dana-Farber. ‘Patients generally respond well to initial chemotherapy, but the disease almost always returns. Less than 5 percent of patients are alive five years after being diagnosed with the disease.’ “

Amrubicin Edges Topotecan for Survival in Refractory SCLC

“Amrubicin failed to improve survival over topotecan as second-line therapy for patients with sensitive small-cell lung cancer (SCLC), according to results of a new randomized phase III trial. There was, however, a small overall survival benefit seen in patients with refractory disease.

“ ‘SCLC is the most aggressive type of lung cancer,’ wrote researchers led by Joachim von Pawel, MD, of Asklepios Fachkliniken München-Gauting in Germany. ‘Despite encouraging phase II results for many targeted therapies and newer chemotherapeutic agents, current large phase III trials have failed to show improvement compared with standard of care.’ Currently, topotecan is the only approved drug for second-line therapy in SCLC patients sensitive to initial treatment; earlier work suggested the third-generation anthracycline and topoisomerase II inhibitor amrubicin could have strong activity in these patients.

“The new study included 637 patients with refractory or sensitive SCLC, assigned 2:1 to amrubicin or topotecan. The median overall survival was 7.5 months with amrubicin and 7.8 months with topotecan, for a hazard ratio of 0.880 (95% CI, 0.733-1.057; P = .170).”

Molecular Tumor Markers Could Reveal New Therapeutic Targets for Lung Cancer Treatment

The gist: New research looking into tumor mutations in small cell lung cancer (SCLC) and neuroendocrine tumors (NET) may open up new drug options to treat these conditions. Drugs called targeted therapies have been developed to treat people with tumors that have certain genetic mutations. Several targeted therapies are available for people with non-small cell lung cancer (NSCLC). But so far, targeted therapies have not been very useful in SCLC. Now, researchers have found that some SCLC and NET tumors may share some tumor mutations with NSCLC tumors. Theoretically, a patient with SCLC or NET could ask their oncologist for molecular testing to see whether their tumor(s) could potentially be treated off-label with an existing NSCLC drug. To learn more about SCLC treatment, see our Need to Know blog.

“Analysis of 607 small cell lung cancer (SCLC) lung tumors and neuroendocrine tumors (NET) identified common molecular markers among both groups that could reveal new therapeutic targets for patients with similar types of lung cancer, according to research presented today at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. The Symposium is sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), the International Association for the Study of Lung Cancer (IASLC) and The University of Chicago Medicine.

“This study examined the clinical specimens of 607 total cases of SCLC tumors (375) and lung NET (232), which included carcinoid, atypical carcinoid and large-cell neuroendocrine tumors. Biomarker testing was achieved through a combination of DNA sequencing (Next-Generation Sequencing (NGS) or Sanger-based); immunohistochemistry (IHC) to identify which proteins are present; and in situ hybridization (ISH) testing, a form of gene amplification, to determine if any of the markers that can cause cancer cells to grow or to become resistant to treatment are present…

” ‘Even cancers that appear to be very similar can be dramatically different at the molecular level, and these differences may reflect unique vulnerabilities that could positively impact therapeutic options and decisions,’ said Stephen V. Liu, MD, senior study author and Assistant Professor of Medicine in the Division of Hematology/Oncology at Georgetown University’s Lombardi Comprehensive Cancer Center in Washington, DC. ‘We are pleased that this research confirms these rarer subtypes; it calls for additional investigation on a larger scale. Once confirmed, molecular profiling of small cell tumors and NET could become standard, as it is currently for non-small cell lung cancers, which will be especially important as more molecularly targeted chemotherapy agents are developed.’ “

Cancer Care: Post-Surgical Mortality Risk, Tumor Boards (CME/CE)

Note: This article includes three different stories for cancer patients. Two are excerpted below.

“Patients who died within a month of cancer surgery had unfavorable social and demographics that appeared to confer high risk, a review of records for more than 1 million people showed.

“The patients at highest risk of early death tended to be unmarried, uninsured, nonwhite, male, older, less education, poorer, and to have more advanced disease at surgery. The results suggest that reducing sociodemographic disparities in cancer care, including access, has the potential to improve cancer outcomes, Brandon A. Mahal, a medical student at Harvard University, reported at the American Society of Clinical Oncology Quality Care Symposium…

“Patients with advanced colorectal or small cell lung cancer (SCLC) had better survival when their oncologists participated at least weekly in tumor board meetings, according to a study of 4,600 patients and 1,600 oncologists.

“Frequent oncologist participation in tumor boards was associated with about a 30% reduction in the mortality hazard for patients with stage IV colorectal cancer and about a 40% reduction in the hazard for extensive SCLC. Oncologists who participated in weekly tumor boards also were more likely to discuss and refer patients to clinical trials and to pursue curative surgery for patients with early-stage non-small cell lung cancer (NSCLC).

” ‘Patients with disease subtypes for which we found a link between physician tumor board participation and improved outcomes may want to ask their doctor if their case will be reviewed at a multidisciplinary meeting,’ Kenneth L. Kehl, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a statement.

” ‘However, this was not a randomized study; as there were few associations overall between tumor boards and patient survival, our findings cannot demonstrate conclusively that physician tumor board participation directly affects patient outcomes.’ ”

Aldoxorubicin Receives FDA Orphan Drug Designations for Glioblastoma, Small Cell Lung Cancer, and Ovarian Cancer

The gist: When a newly developed drug for a rare (“orphan”) disease seems particularly promising for patients, the U.S. Food and Drug Administration (FDA) may choose to grant it “orphan drug designation.” The designation removes certain barriers that might otherwise keep a drug company from being able to successfully develop and profit from the drug in the U.S. A new drug called aldoxorubicin has just received an orphan drug designation for the treatment of small cell lung cancer (SCLC), glioblastoma multiforme, and ovarian cancer. Aldoxorubicin is a special version of the chemotherapy drug doxorubicin. It allows for higher doses of doxorubicin with fewer side effects.

“The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designations to aldoxorubicin in three indications: glioblastoma multiforme, small cell lung cancer, and ovarian cancer. Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to albumin, allowing greater doses of the chemotherapeutic agent to be administered while reducing its toxic side effects.

“Aldoxorubicin is currently being studied in a global phase III clinical trial evaluating the efficacy and safety of aldoxorubicin as a second-line treatment for patients with soft-tissue sarcoma. CytRx, a biopharmaceutical research and development company, is also evaluating aldoxorubicin in two phase II clinical trials, one in patients with late-stage glioblastoma multiforme and the other in HIV-related Kaposi’s sarcoma. A global phase IIb trial in patients with relapsed small cell lung cancer is expected to commence later this month, and the company is undertaking a phase Ib combination study of aldoxorubicin plus gemcitabine as a potential precursor to a trial in relapsed ovarian cancer.”