Positive data presented at recent LC conference

At the recent AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer in Coronado, CA, many positive advances were presented, including a new study, which suggested that retreating non-small cell lung cancer (NSCLC) patients with AstraZeneca's Iressa (gefitinib) could have a beneficial effect, Phase II study results of ASA404 (vadimezan) in patients with either squamous or non-squamous NSCLC and preclinical results showing that Synta Pharmaceuticals' STA-9090 is active against 100 per cent of all NSCLC cell lines tested.

With regard to the gefitinib study, researchers evaluated 15 patients who were retreated with the drug after more than one cycle of chemotherapy for advanced or metastatic NSCLC. Among the six patients who had showed partial response (PR) with initial gefitinib treatment, two patients showed an additional PR and three continued to show stable disease (SD). Among the nine patients who showed SD with the initial gefitinib treatment, two patients showed PR and three showed SD. The overall disease control rate was 66.7 per cent.

Separately, ASA404 showed promise in patients with either squamous or non-squamous NSCLC. These results support ongoing Phase III studies of the drug in NSCLC. Under development by Novartis, which licensed the drug from Antisoma, ASA404 has a unique mechanism of action against a tumour's blood supply. The product has been shown to cause selective disruption of the established tumour vasculature, inhibition of tumour blood flow and tumour necrosis. This unique mechanism of action could provide an option for patients with either squamous or non-squamous NSCLC. Treatment options for patients with advanced-stage NSCLC are limited, particularly for those with squamous histology where some treatments exhibit limited efficacy or serious side effects.

Further, preclinical results showed that STA-9090, a potent, synthetic inhibitor of heat shock protein 90, demonstrated potent activity against 100 per cent of all NSCLC cell lines tested, including those with EGFr, HER2 or KRAS mutations, including the EGFr T790 mutation that is present in approximately 50 per cent of cases of erlotinib or gefitinib resistance. Synta is currently enrolling patients in a single-arm, open-label, single-agent, Phase II study of STA-9090 in patients with Stage IIIb or IV NSCLC, with patient cohorts defined by the genetic profile of their tumours.

STA-9090 potently inhibited cell proliferation in 24 out of 24 human NSCLC lines tested, irrespective of EGFr, HER2 or KRAS mutational status. In vivo, STA-9090 stopped tumour growth in both erlotinib-sensitive and -resistant NSCLC xenograft models. In addition, in a HER2-positive adenosquamous LC study, three out of four animals treated with STA-9090 experienced partial responses, as measured by MRI. Dr Vojo Vukovic, Chief Medical Officer of Synta, stated: "taken together, the in vitro and in vivo results presented at this conference demonstrate the potency, broad activity and safety profile of STA-9090, both as a single agent and in combination with taxanes in NSCLC."

Alice Rossiter
Editor, Cancer Drug News