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.”


ELCC 2014 News: Cabazitaxel Fails to Meet the Primary Endpoint in a Randomised Phase II Study in SCLC Patients

“Cabazitaxel failed to meet a primary endpoint of showing superior progression-free survival (PFS) and additionally showed less favourable median overall survival (OS) compared to topotecan in an international, randomised open-label phase II trial performed in patients with small-cell lung cancer (SCLC), who had progressed during or after first-line platinum-based chemotherapy. The results were presented by Dr Tracey Evans of the Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, USA in a proffered papers session at the 4th European Lung Cancer Conference (26-29 March 2014, Geneva, Switzerland).”

Editor’s note: This trial found disappointing results for the drug cabazitaxel in treating small cell lung cancer (SCLC). To read about promising SCLC treatments, see this blog feature.


Immune System-Boosting Treatments Show Long-Sought Successes for Lung Cancer Patients


In the past 2 years, cancer treatments known as immune therapies have become all the rage. However, they have actually been explored for decades, particularly in melanoma, and have produced some notable successes. Now, immune therapies are showing more and more promise for lung cancer. Continue reading…


New Clinical Trial for SCLC Now Enrolling Patients

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.