AstraZeneca eyes early 2020 FDA verdict on Imfinzi in SCLC

Will go head-to-head with rival Roche's Tecentriq if approved

The FDA has started a priority review of AstraZeneca’s immuno-oncology drug Imfinzi as a first-line treatment for small cell lung cancer (SCLC), with a decision due in the first quarter of next year.

If approved, Imfinzi (durvalumab) will go head-to-head with Roche’s Tecentriq (atezolizumab), which was approved for previously-untreated SCLC in the US earlier this year.

SCLC is less common than non-small cell lung cancer (NSCLC) but is a particularly aggressive form, growing more quickly and spreading to other parts of the body earlier.

It is fairly responsive to chemotherapy and radiotherapy, but relapse rates are high and median survival low – often a year or less in extensive-stage disease where the tumour has spread beyond the lung and adjacent lymph node at diagnosis.

Imfinzi’s marketing application is centred on the results of the CASPIAN trial, which showed that adding the PD-L1 inhibitor to standard chemotherapy with etoposide and either cisplatin or carboplatin reduced the risk of death by 27% compared to chemo alone.

The median overall survival (OS) was 13 months for Imfinzi, versus just over 10 months for the control group, and after 18 months 34% of patients on AZ’s drug were still alive compared to 24.7% of those only receiving chemo.

The performances of Imfinzi and Tecentriq in this patient group look similar on paper, with Roche’s drug extending OS to 12.3 months compared to 10.3 months with chemo alone, but AZ has argued in the past that Imfinzi’s data points to a more durable response.

It has also said that as CASPIAN included both carboplatin and cisplatin groups, while Roche’s IMpower133 only included carboplatin, Imfinzi caters for differing clinical practice among oncologists. The regimen is also administered every four weeks rather than every three for Tecentriq, and that creates a trade off between less frequent clinic visits and closer patient monitoring.

It is clear that having two positive trials has reassured cancer specialists that there is value in combining immunotherapy with chemotherapy in SCLC, and more could be on the way soon.

Merck & Co/MSD’s PD-1 inhibitor Keytruda (pembrolizumab) – already dominating NSCLC therapy – is already approved for third-line SCLC treatment and is in a first-line phase 3 trial (KeyNote-604) alongside chemo that is nearing completion.

Meantime, Bristol-Myers Squibb also has a phase 2 trial in this setting with its PD-1 inhibitor Opdivo (nivolumab) – also approved for third-line use in SCLC.

CASPIAN includes a third arm that is testing Imfinzi alongside AZ’s experimental CTLA4 inhibitor tremelimumab, which would allow patients to sidestep chemo entirely, but data from that isn’t expected to be available until next year.

BMS tested Opdivo with its already-approved TLA4 inhibitor Yervoy (ipilimumab) as a maintenance therapy after chemotherapy for extensive-stage SCLC in the CheckMate-451 trial, but that wasn’t able to show an improvement in survival compared to placebo.