“Adding palifosfamide to carboplatin and etoposide failed to improve survival over the latter two agents alone in patients with extensive stage (ES) small-cell lung cancer (SCLC), according to a new study.
” ‘Platinum doublet chemotherapy has been the standard of care first-line regimen in patients with ES SCLC for the last 3 decades,’ wrote study authors led by Shadia I. Jalal, MD, of the Indiana University Melvin and Bren Simon Cancer Center in Indianapolis. ‘Unfortunately, disease relapse occurs in all patients, and second-line chemotherapy options lead to short responses. Novel first-line therapies continue to be urgently needed.’ ”
“A phase I/II study will explore the delta-like protein 3 (DLL3)-targeted antibody-drug conjugate rovalpituzumab tesirine (Rova-T) with the PD-1 inhibitor nivolumab (Opdivo) alone or in combination with the CTLA-4 inhibitor ipilimumab (Yervoy) for patients with relapsed extensive-stage small cell lung cancer (SCLC).
“AbbVie, the developer of rovalpituzumab tesirine, and Bristol-Myers Squibb, the company marketing nivolumab and ipilimumab announced the phase I/II study in a joint press release. As single-agents, rovalpituzumab tesirine and nivolumab have each demonstrated promising early findings for patients with SCLC. Additionally, nivolumab plus ipilimumab sparked promising response rates and overall survival (OS) findings. Data for the 3 agents were recently presented at the 2016 ASCO Annual Meeting.”
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“OncoMed Pharmaceuticals Inc. (NASDAQ: OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported new biomarker and updated clinical data for the company’s Phase 2 anti-Notch2/3 therapeutic candidate, tarextumab (OMP-59R5). These data show the potential of Notch3 overexpression as a prognostic factor in small cell lung cancer and update OncoMed’s Phase 1b results for tarextumab in combination with standard-of-care chemotherapy for the first-line treatment of patients with extensive-stage disease. Anne Chiang, M.D., Ph.D., of the Yale School of Medicine, will present these data in a mini-oral presentation this afternoon at the 16th World Lung Conference on Lung Cancer.
” ‘Notch is known to be a fundamental cancer stem cell pathway driving the initiation and spread of tumors. Notch3 in particular has been associated with poor prognosis in a variety of solid tumor types, including pancreatic, breast and ovarian cancers,’ said Dr. Chiang. ‘Our analyses of small cell lung cancer patient tumors demonstrate that Notch3 overexpression in extensive-stage small cell lung cancer tumors is common and may be associated with poor survival. This is the first time that Notch3 tumor expression has been tested in small cell lung cancer and associated with poor patient outcomes.’ “
“The use of maintenance sunitinib improved progression-free survival (PFS) over placebo among patients with untreated extensive-stage small-cell lung cancer (SCLC) in a new phase II study.
“ ‘Most of the 30,000 patients newly diagnosed each year with SCLC in the United States have extensive-stage disease,’ wrote study authors led by Neal E. Ready, MD, PhD, of Duke University Medical Center in Durham, North Carolina. ‘Despite achieving good disease control initially, patients with SCLC usually experience relapse within 6 months of first-line chemotherapy and often do not respond to subsequent chemotherapy.’
“In previous studies, maintenance chemotherapy after standard platinum-based therapy did not show any overall survival benefit. The new study aimed to test whether sunitinib, a small-molecule tyrosine kinase inhibitor that inhibits VEGF receptors and other targets. Results of the new study were published online ahead of print in the Journal of Clinical Oncology.
“The study enrolled a total of 144 patients, 49 of whom progressed or did not complete induction chemotherapy; 95 patients were randomly assigned to a placebo maintenance therapy group (46 patients) or a sunitinib maintenance therapy group (49 patients), and five patients on each arm did not receive the maintenance therapy. Sunitinib patients received 37.5 mg per day until progression.”
The gist: This article discusses the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to examine the effectiveness of a new treatment for extensive-stage small cell lung cancer (ES-SCLC). The treatment adds thoracic (chest) radiotherapy to standard treatment with chemotherapy and cranial (head) radiotherapy. Patients in the trial who received the new treatment had significantly improved outcomes.
“The addition of thoracic radiotherapy to chemotherapy and prophylactic cranial irradiation significantly improved 2-year survival and other outcomes in patients with extensive-stage small-cell lung cancer (ES-SCLC), according to results of a new phase III randomized trial.
“Survival for ES-SCLC is poor, and has improved little in recent decades,” wrote study authors led by Ben J. Slotman, MD, of VU University Medical Center in Amsterdam. Though previous research has shown prophylactic cranial irradiation can improve outcomes, intrathoracic disease often remains a problem. In this study, the investigators compared 247 patients who received thoracic radiotherapy with 248 patients who did not; all patients underwent prophylactic cranial irradiation. The results were published online ahead of print on September 14 in the Lancet.
“The median overall survival at 1 year was no different between the groups, at 33% in the thoracic radiotherapy group and 28% in the control patients, for a hazard ratio (HR) of 0.84 (95% CI, 0.69-1.01; P = .066). But a secondary analysis of 2-year survival did show improvement, at 13% in the radiotherapy group vs 3% in the control patients (P = .004). The number of patients needed to treat to avoid one death was 10.6.”
“Thoracic radiotherapy along with prophylactic cranial irradiation (PCI) significantly prolonged progression-free and overall survival in patients with extensive-stage small-cell lung cancer, according to results of a new study presented at ASCO.
“Ben Slotman, MD, PhD, of VU University Medical Center in Amsterdam, presented the study and said that previous work had shown that PCI could improve both symptomatic brain metastases and overall survival at 1 year. ‘In that study, we also noticed that the vast majority of patients after chemotherapy had intrathoracic disease’ and intrathoracic progression, he said, which was the impetus for the new study using thoracic radiotherapy.”
Editor’s note: To learn more about new prospects for treating small cell lung cancer (SCLC), see our two-part blog feature on the topic.
“A combination of amrubicin and cisplatin was inferior to irinotecan and cisplatin in chemotherapy-naïve patients with extensive disease small-cell lung cancer (SCLC) in a phase III trial conducted in Japan. The irinotecan regimen remains the standard treatment for these patients in that country.
“SCLC accounts for 13% of all new cases of lung cancer, and more than half of those patients present with extensive disease. Though SCLC can be very sensitive to chemotherapy, authors of the new study wrote that “rapid emergence of clinical drug resistance has resulted in poor prognosis, with almost all such patients dead with 2 years of initial diagnosis.” Investigators led by Miyako Satouchi, MD, PhD, of the Hyogo Cancer Center in Akashi, Japan, tested the amrubicin and cisplatin combination against irinotecan and cisplatin in 284 patients; results were published online ahead of print on March 17 in the Journal of Clinical Oncology.”
While medical research has produced significant treatment innovations for many cancer types, so far little has changed for small cell lung cancer (SCLC). Current treatment guidelines recommend chemotherapy with etoposide (Etopophos) and cisplatin (Platinol), drugs than are more than 30 years old. Relapse is common, and survival rates remain low. Now, the new PINNACLE clinical trial will investigate a new drug against SCLC. Patients with extensive-stage SCLC who have never received any other cancer treatment will be treated with Etopophos and Platinol either by themselves or in combination with the new drug, OMP-59R5. The drug acts by inhibiting NOTCH, a protein involved in cell development and growth that plays a role in various cancers. For more information, call 646-888-4203.
Small cell lung cancer (SCLC) usually responds well to initial chemotherapy, but frequently relapses within a short time. Maintenance therapy with the drug sunitinib (Sutent) may delay relapse and improve outcomes for SCLC patients, results from a recent phase II clinical trial suggest. Patients with extensive-stage SCLC who had responded to initial chemotherapy were given either Sutent as maintenance therapy or a placebo. Sutent, a tyrosine kinase inhibitor (TKI) that blocks several proteins involved in SCLC, prolonged the time without cancer progression (3.2 months on average, compared to 2.3 months in the placebo-treated patients). Patients receiving Sutent also tended to have longer overall survival (8.9 months vs 6.9 months with placebo), although this finding was not clear enough to determine whether it was due to chance. The survival difference between patient groups may have been smaller because placebo-treated patients whose cancer relapsed were allowed to switch to Sutent, suggesting that Sutent may actually have more definite effects on patient survival.