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Can AZ’s Imfinzi challenge Tecentriq in small cell lung cancer?

New data shows improvement in overall survival


AstraZeneca has put the flesh on the bones of its CASPIAN trial of immuno-oncology drug Imfinzi in advanced small cell lung cancer (SCLC), revealing the drug improved overall survival by 27%.

The drugmaker first reported the top-line data from the phase 3 trial in June, saying that it would be used to seek approval of Imfinzi (durvalumab) in combination with chemotherapy in previously-untreated patients with extensive-stage SCLC, said to be the most aggressive for of lung cancer.

At the World Conference on Lung Cancer (WCLC), lead investigator Luis Paz-Ares of Hospital Universitario Doce de Octubre in Madrid told delegates that Imfinzi plus etoposide-based chemotherapy achieved a median OS of 13.0 months, which compared to 10.3 months with chemo alone.

The big question is whether the CASPIAN data is compelling enough to challenge Roche’s PD-L1 inhibitor Tecentriq (atezolizumab), which was approved for first-line SCLC in the US in March.

On the face of it the results are similar, with Roche’s drug extending survival to 12.3 months when added to chemotherapy versus 10.3 months with chemo alone in the IMpower133 trial, but AZ’s position is that its drug has also shown an improved durability of response.

After 12 months progression-free survival (PFS) was 17.5% compared to 4.7% with chemo, with the duration of response also better at 22.7% versus 6.3% respectively. After 18 months, 33.9% of patients on Imfinzi were still alive, compared to 24.7% of the control group.

AZ also says that unlike IMpowerr133, CASPIAN looked at multiple chemotherapy options, including combinations with either cisplatin or carboplatin, giving physicians more choice and catering for varying changes in clinical practice. It also has stronger data in patients whose cancer has spread to the central nervous system.

The discussant for the study at WCLC – Myung-Ju Ahn of Sungkyunkwan University in South Korea – said that the results looked consistent with IMpower133 and underscore that checkpoint inhibition improves on chemotherapy.

For now, it looks like AZ can compete with Roche on an equal footing at least in first-line SCLC if it secures approval for Imfinzi in this setting. Both companies will however be looking over their shoulders at Merck & Co/MSD – already reigning supreme in NSCLC – which has approval for third-line SCLC and has a first-line phase 3 trial nearing completion.

SCLC is less common than non-small cell lung cancer (NSCLC) but tends to be more aggressive, growing more quickly and spreading to other parts of the body earlier. The five-year survival rate with this form of cancer is as low as 6%, with two-thirds of patients having advanced disease at the time of diagnosis.

CASPIAN also included an arm that received Imfinzi, chemo and AZ’s experimental CTLA4 inhibitor tremelimumab, but that data has yet to mature and is expected to be ready next year. So far, adding tremelimumab to Imfinzi hasn’t been able to improve efficacy in trials.

Article by
Phil Taylor

10th September 2019

From: Research



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