Lynparza is not the most important ingredient of Astrazeneca’s reboot as an oncology company, but its expansion does not hurt. Full data from the Olympiad trial presented at Asco give the Parp inhibitor a shot at becoming the first drug in its class to move into breast cancer.
Parp inhibition is shaping up as an Astra-versus-Tesaro affair, as the smaller biotech chose to play up an immuno-oncology combination in breast cancer in its investor presentation on the sidelines of Asco. In possession of its own immuno-oncology arsenal, Astra is in a position to counterpunch – Lynparza plus the PD-L1 antibody Imfinzi will soon enter a phase II trial in triple-negative disease.
Better than chemo
Olympiad was a trial in Her2-negative metastatic breast cancer patients with BRCA mutations that compared Lynparza against physicians’ chemotherapy choice – patients could have received no more than two lines of chemotherapy before entering the trial. Patients taking Lynparza had a significant 42% reduced risk of progression, with seven months of progression-free survival compared with 4.2 months for patients treated with chemotherapy.
A better side-effect profile was also on Lynparza’s side – 37% had grade 3 or greater adverse events compared with 51% of patients on chemotherapy. This prompted the lead investigator, Mark Robson of Memorial Sloan Kettering Cancer Center, to declare that the drug would be best used early in the course of the disease to preserve patient quality of life.
Lynparza was approved for use in ovarian cancer in 2014, and that indication will account for nearly 72% of its forecast $1.2bn in sales in 2022, according to EvaluatePharma’s consensus of sellside analyst forecasts. Almost the same is true for Tesaro, whose Zejula is forecast to achieve $1.3bn in sales, 76% of which will be in ovarian cancer.
Breast cancer is expected to represent a growing share, accounting for 14% of Lynparza’s sales in 2022 and 21% of Zejula’s.
Combo is the thing
With the onrush of immuno-oncology, targeted monotherapies seem terribly old-fashioned, and that is probably what Tesaro was thinking when it played up early data from the Topacio trial of Zejula with Keytruda in triple-negative breast cancer or ovarian cancer at its off-site investor event during Asco.
This is part of a sector-wide effort to test projects in combination with agents active on the PD-1/PD-L1 pathway (Immuno-oncology combinations surge as sector seeks the fairy dust, June 1, 2017).
The need to test combinations was a point on which Asco's president, Daniel Hayes, an oncologist the University of Michigan, focused. While Lynparza was able to improve progression free survival, he pointed out that the survival curves “still come together”, sparking a need to understand resistance.
Dr Robson said combinations with chemotherapy might be tricky because of overlapping bone marrow toxicity. In combination with other targeted agents or immuno-oncology projects, on the other hand, might have a better side-effect profile, he said.
Thus Tesaro’s desire to talk about the Topacio trial at its investor meeting, in which early data in breast cancer showed stable disease in one of the five patients with triple-negative breast cancer. Its monotherapy breast cancer trial called Bravo not due to read out for a few months.
Astra has only recently begun viewing Lynparza as a potential immuno-oncology combination agent. Just 12 days ago it filed a Clinicaltrials.gov entry for a study called Dora that will combine Lynparza and Imfinzi in triple-negative breast cancer.
Nevertheless, Astra is in a position to file first to add breast cancer to the label of its Parp, and oncologists in theory could begin using Lynparza off-label before any regulatory deadline. The duration of this advantage will be determined by findings from immuno-oncology trials, which could come very quickly.