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.”


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).”


FDA Approves Avastin to Treat Patients with Aggressive and Late-Stage Cervical Cancer

“The U.S. Food and Drug Administration today approved a new use for Avastin (bevacizumab) to treat patients with persistent, recurrent or late-stage (metastatic) cervical cancer.

“Cervical cancer grows in the tissues of the lower part of the uterus known as the cervix. It commonly occurs when human papillomaviruses (HPV), a virus that spreads through sexual contact, cause cells to become cancerous. Although there are two licensed vaccines available to prevent many types of HPV that can cause cervical cancer, the National Cancer Institute estimates that 12,360 American women will be diagnosed with cervical cancer and 4,020 will die from the disease in 2014.

“Avastin works by interfering with the blood vessels that fuel the development of cancerous cells. The new indication for cervical cancer is approved for use in combination with chemotherapy drugs paclitaxel and cisplatin or in combination with paclitaxel and topotecan.”


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.”


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.


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.


Gene Expression Data Integration to Squamous Cell Lung Cancer Subtypes Reveals Drug Sensitivity

We analysed RNAseq data of 178 squamous cell lung cancer (SqCC) tumour samples and characterised the features of the different SqCC subtypes to define signature genes and pathway alterations specific to each subtype. Further, we compared the gene-expression features of each molecular subtype to specific time points in models of airway development. We also classified SqCC-derived cell lines and their reported therapeutic vulnerabilities.

Compared with the other three subtypes of cell lines, the secretory-type cell lines were significantly less sensitive to the five most effective drugs (Panobinostat, 17-AAG, Irinotecan, Topotecan and Paclitaxel), possibly because of their low proliferation activity.


Avastin-Containing Chemotherapy May Be Safe in Lung Cancer Patients with Brain Metastases

Bevacizumab (Avastin), which is approved for treatment of a number of advanced-stage cancer types, is commonly avoided in patients with brain metastases (cancer that has spread to the brain) because of fear of brain hemorrhages (bleeding in the brain). A retrospective study of 52 patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy containing Avastin found no cases of serious bleeding events and no significant differences in survival or treatment side effects between patients with or without brain metastases. Avastin may therefore be a safe treatment option in NSCLC with brain metastases.

Research paper: https://www.jstage.jst.go.jp/article/acrt/20/2/20_47/_pdf


Overexpression of IGF1R and EGFR Genes May Worsen Lung Cancer Prognosis

The roles of the genes IGF1R and EGFR in lung cancer were examined in patients with non-small cell lung cancer (NSCLC) who had their primary tumor surgically removed. Patients whose tumors had increased expression of both IGFR1R and EGFR were more likely to experience recurrence of the cancer after a shorter amount of time and had shorter survival times after surgery. This finding suggests that concurrent overexpression of IGF1R and EGFR is a negative prognosis factor in NSCLC and may indicate patients who are more likely to benefit from novel treatments with IGF1R inhibitors.

Research paper: http://link.springer.com/article/10.1007/s00280-012-2056-y/fulltext.html