The torrent of data released at the American Society of Clinical Oncology in Chicago this past week is shifting the balance of power among makers of breast cancer treatments.
Roche Holding Ltd., long the leader in breast cancer with its Herceptin medicine and newer Perjeta, saw its stock slide as data presented at the meeting failed to impress some investors and oncologists.
Meanwhile, AstraZeneca PLC's Lynparza study results were unanimously viewed as a positive, and Merck & Co. Inc.'s Keytruda has a chance to add the disease to its long list of approved indications, according to equity analysts. Findings from Eli Lilly & Co. and Pfizer Inc. left questions to be answered in future trials.
A negative editorial on Roche results
When added to Herceptin, Roche's Perjeta reduced the risk of breast cancer recurrence or death by 19% among patients with HER2-positive early breast cancer in a trial designed to earn approval for a combination of the two established breast cancer medicines, the company reported June 5. The absolute risk reduction was less than 1 percentage point — 94.1% of patients who received Perjeta were cancer-free three years after surgery, compared to 93.2% of those who did not receive it.
Oncologist Kathy Miller of the Indiana University Melvin and Bren Simon Cancer Center in Indianapolis said the increased side effects, such as "cardiac toxic effects," do not justify the use of Perjeta, given the small incremental benefits.
"It simply is not feasible to add more and more therapy for all patients with HER2-positive disease who are selected only on the basis of anatomy. The toxic effects (and cost) are too great for too many to benefit too few," she wrote in a June 5 editorial in the New England Journal of Medicine.
Roche defended the data during an investor presentation by pointing to a slightly larger risk percentage reduction among certain patient subgroups, according to Jefferies analyst Jeffrey Holford. In addition, the data sparked "fierce debate about cost-effectiveness at ASCO (which is par for the course of late)," Holford wrote in a June 6 analyst note.
Holford wrote June 5 that the data appear toward the "bottom end" of Wall Street expectations. Roche's shares ended the June 6 trading session down more than 5%.
AstraZeneca, Merck gain strength at ASCO
Wall Street analysts were more impressed when AstraZeneca revealed on June 4 that its ovarian cancer medicine Lynparza reduced the risk of breast cancer death or tumor progression by 42% compared to chemotherapy.
"Not only did the data represent another watershed for the advance of genomic driven diagnosis and therapy in cancer treatment, the data validated our view that the asset represents a 'pipeline in drug' opportunity," Barclays analyst Emmanuel Papadakis wrote in a June 5 note. The expected breast cancer indication expansion from the U.S. Food and Drug Administration will turn Lynparza from a minor opportunity in ovarian cancer alone, to a reasonably significant asset over time, he said.
While the data was "solid," the chemotherapy comparison arm used older therapies "and therefore may have provided an easy comparison," Cowen analyst Steve Scala said in a note to investors.
Merck released trial data showing that when Keytruda was added to standard breast cancer therapy in a preoperative setting, the proportion of patients with no residual cancer following treatment tripled to 60% among patients with triple-negative breast cancer, a version of the disease that does not exhibit two hormone receptors and the HER2 protein. The response rate more than doubled to 34% among HER2-negative patients who tested positive for a hormone receptor.
"We are highly confident that Keytruda will ultimately move into this potentially large opportunity," wrote Credit Suisse's Vamil Divan in a June 5 analyst note, noting that the company said a filing for the expanded indication is not possible with the current data set.
Leerink's Seamus Fernandez concurred, writing that the data suggest an opportunity to expand into HER2-negative breast cancer, including triple-negative breast cancer.
Both companies are targeting triple-negative breast cancer via their indication expansions. The unmet need among such patients is high because they have not benefited from the many new therapies targeting the HER2-positive variant of the disease, said AstraZeneca's vice president of U.S. oncology Michelle Werner during a prior interview at ASCO.
Eli Lilly, Pfizer data inconclusive
Eli Lilly's phase 3 breast cancer candidate posted a median disease progression-free survival of 16.4 months when used with chemotherapy, about seven months better chemotherapy alone. Rates of severe diarrhea were reduced by lowering the starting dose to 150 milligrams, Jefferies' Holford said.
"With discontinuation rates due to diarrhea now at only 1.6%, this no longer appears to be a major barrier to adoption, albeit still a nuisance that has to be more than compensated for by better efficacy in our view," he wrote in June 4 note.
Data showing whether the candidate for HER2-negative, hormone receptor-positive patients has better efficacy than Pfizer's competing Ibrance will probably be made available at the European Society of Medical Oncology conference in September, according to the analyst.
Pfizer's phase 2 breast cancer candidate, talazoparib, reduced tumor size by a clinically meaningful amount in 28% of patients. Inherited via Pfizer's $14 billion acquisition of San Francisco-based Medivation, it would compete directly with Lynparza and recently approved medicines from Tesaro Inc. and Clovis Oncology if approved.
Credit Suisse's Divan is waiting for the candidate's phase 3 data but is left wondering "how talazoparib will differentiate itself in an increasingly crowded PARP market," according to a June 3 note.