Thoracic RT Improves Long-Term Survival in Extensive-Stage SCLC

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.”


Some Lung Cancer Patients Could Live Longer When Treated with New Radiotherapy Strategy

The gist: A type of radiation treatment called thoracic radiotherapy may help some lung cancer patients live longer after chemotherapy. That was the conclusion of a recent clinical trial—a research study with volunteer patients.

“The authors say that as the thoracic radiotherapy is well tolerated, it should to be routinely offered to all SCLC patients with extensive disease whose cancer responds to chemotherapy.

“SCLC is an aggressive cancer that accounts for about 13% of all lung cancers. The majority of patients present with extensive disease that has spread to other areas of the body.

” ‘In recent years, we have made some progress in improving survival by giving prophylactic cranial radiotherapy (radiation to the head to reduce the risk of the cancer spreading to the brain) after chemotherapy, and this is now considered the standard of care. However, survival for patients with extensive disease remains poor (2-year survival of less than 5%) and the likelihood of the cancer recurring and spreading to other parts of the body remains high’, explains Ben Slotman, lead author and Professor of Radiation Oncology at the VU University Medical Center in Amsterdam, Netherlands…

“Writing in a linked Comment, Jan P van Meerbeeck from Ghent and Antwerp University in Belgium and David Ball from The University of Melbourne in Australia point out, ‘Refreshingly, the radiotherapy in Slotman and colleagues’ study was not technically complex and it would be easy to provide at low cost in even the most modestly resourced radiotherapy departments.’ “


Novel Oncogenic RET Mutation Found in Small Cell Lung Cancer

Editor’s note: An oncologist will sometimes test a patient’s tumor for specific mutations in order to decide what the best treatment options are. Tumors that have certain mutations can sometimes be treated with certain so-called targeted therapy drugs. This approach has worked well for many people with non-small cell lung cancer (NSCLC). However, there are no FDA-approved targeted therapies for small cell lung cancer (SCLC). A new discovery might change that. Researchers found a mutation called RET M918T in a metastatic SCLC tumor. Two targeted drugs were found to fight against tumor cells with the mutation in the lab. The drugs—ponatinib and vandetanib—are already FDA-approved to treat other types of cancer.

“For the first time, an oncogenic somatic mutation at amino acid 918 in the rearranged during transfection protein has been identified in small cell lung cancer tumors and enforced expression of this mutation within small cell lung cancer tumor cell lines produced increased intracellular signaling and cell growth.

“SCLC is a highly malignant form of lung cancer representing 15% of all lung cancers and is strongly associated with tobacco smoking. NSCLC, representing 85% of lung cancer, has been extensively examined for genomic alterations and targeted therapies are approved for patients with certain mutations, however SCLC has not been examined with the same rigor and there are no approved targeted therapies for SCLC.

“Investigators at Case Western University examined 6 SCLC tumors, 3 each from primary and metastatic tumors, for 238 somatic mutations across 19 oncogenes. RET wild type and mutant protein was then overexpressed in SCLC cell lines and these cell lines were examined for cell signaling, cell growth and responsiveness to two tyrosine kinase inhibitors of RET.”


Adding Ziv-Aflibercept to Topotecan Improves Progression-Free Survival but Increases Toxicity in Platinum-Treated Small Cell Lung Cancer

Editor’s note: A recent clinical trial with volunteer patients tested whether a treatment that combines a drug called ziv-aflibercept (Zaltrap) with the drug topotecan would be better than toptecan alone for people with small cell lung cancer (SCLC). All participating patients had previously been treated with platinum-based chemotherapy and had been treated for brain metastases. Patients were randomly assigned to be treated with either topotecan alone, or the topotecan/ziv-aflibercept combination. The researchers found that the combination treatment significantly increased the number of patients who survived three months or more without their disease worsening. However, the combo treatment had worse side effects and did not improve overall survival.

“The phase II Southwest Oncology Group (SWOG) S0802 trial reported in the Journal of Clinical Oncology by Allen et al showed that adding ziv-aflibercept (Zaltrap) to topotecan improved 3-month progression-free survival, but increased toxicity and had no effect on overall survival, in patients with platinum-treated small cell lung cancer (SCLC)…

“In the trial, 189 patients who had experienced disease progression after one line of platinum-based chemotherapy and had treated brain metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, and no recent vascular events or bleeding diatheses were randomly assigned to receive weekly topotecan at 4 mg/m2 with (n = 97) or without (n = 92) ziv-aflibercept at 6 mg/kg every 21 days. Patients were stratified as platinum-refractory (n = 55 vs 51) or platinum-sensitive (n = 42 vs 41). Progression-free survival at 3 months was the primary endpoint.”


New Drug Active Against Most Aggressive Type of Lung Cancer Cells

Cancer cells

Editor’s note: New research has uncovered a potential new treatment option for people with small cell lung cancer (SCLC). A drug called AZD3965 has been shown to be effective in killing SCLC cells in the laboratory and in mice. Scientists also found evidence that the drug would work best in patients who have elevated levels of a protein called MCT1. AZD3965 has been tested and found to be effective for some patients with other cancer types, but it has not yet been tested in people with SCLC in clinical trials.

Excerpt:

“Manchester scientists have shown that a new drug could prove useful in treating small cell lung cancer – the most aggressive form of lung cancer.

“Scientists from the Cancer Research UK Manchester Institute, based at The University of Manchester and part of the Manchester Cancer Research Centre, teamed up with experts at AstraZeneca, as part of a collaboration agreed in 2010, to test a drug – known as AZD3965 – on small cell lung cancer cells.

“The research, published in the journal Clinical Cancer Research, also helps identify which patients are most likely to respond to the treatment.”


Chemo Combo Increases Survival, Toxicity in Sensitive Relapsed SCLC

“Cisplatin, etoposide, and irinotecan outperformed topotecan as second-line chemotherapy in patients with sensitive relapsed small-cell lung cancer (SCLC) in a Japanese trial, though there was substantially increased toxicity with the regimen.

“ ‘Topotecan is the only drug approved in the United States and the European Union for relapsed SCLC,’ said Koichi Goto, MD, PhD, of the National Cancer Center Hospital East in Chiba, Japan. He presented results of the new trial at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. Sensitive relapse refers to cancers that respond to initial chemotherapy and relapse more than 3 months after completion of that therapy, while refractory cancers do not respond initially or relapse within that 3 month window.”

Editor’s note: This story is about a clinical trial with volunteer patients to test a new treatment for small cell lung cancer (SCLC). The new treatment is specifically for people with SCLC who were treated with chemotherapy successfully, but whose cancer returned more than 3 months after chemo—this is known as “sensitive relapsed SCLC.” The new treatment combines three chemo drugs: cisplatin, etoposide, and irinotecan. In the clinical trial, some patients took the chemo combo and some were treated with the chemo drug topotecan, which is a standard treatment for the condition. Patients who took the new treatment lived longer, but they had more toxic side effects than the patients who took topotecan.


Thoracic RT Yields Improved Survival in Extensive-Stage SCLC

“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.


'Liquid Biopsy' Offers New Way to Track Lung Cancer

“Scientists have shown how a lung cancer patient’s blood sample could be used to monitor and predict their response to treatment – paving the way for personalised medicine for the disease.

“The recent study, published in the journal Nature Medicine, also offers a method to test new therapies in the lab and to better understand how tumours become resistant to drugs.

“Small cell lung cancer (SCLC) is an aggressive disease with poor survival and new treatments are desperately needed. In many cases the tumour is inoperable and biopsies are difficult to obtain, giving scientists few samples with which to study the disease.”


Amrubicin and Cisplatin Inferior to Irinotecan Regimen for Small-Cell Lung Cancer

“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.”