- Merck & Co.'s immunotherapy Keytruda looks set to take a more commanding position as a first-line treatment of choice for metastatic lung cancer, posting impressive clinical results Sunday that show the drug can extend survival in a broader range of patients than previously shown.
- In a study known as KEYNOTE-042, patients treated with Keytruda monotherapy lived a median of between four and eight months longer than those given chemotherapy, with benefit observed across PD-L1 expression levels greater than 1%.
- Data from another study, also presented Sunday at the annual meeting of the American Society of Clinical Oncology (ASCO), demonstrated combining Keytruda with chemotherapy cut the risk of death by 36% over just chemo in patients with the less common squamous form of non-small cell lung cancer (NSCLC).
For the second major cancer conference in a row, Merck's data from Keytruda outshone results from a competitor.
In April, the pharma wowed researchers attending the American Association of Cancer Research meeting with data showing Keytruda added to chemotherapy cut the risk of death by 51% in patients with non-squamous NSCLC. The impressive results largely stole the spotlight from Bristol-Myers Squibb, which had unveiled an important update of its own for its lung cancer combo of Opdivo (nivolumab) and Yervoy (ipilimumab).
Two months on, it's Roche's turn. The Swiss pharma came into ASCO with an anticipated late-breaking abstract comparing a chemo combination involving its checkpoint inhibitor Tecentriq to chemo alone in squamous NSCLC. Tecentriq, when paired with three other agents, delivered a 29% reduction in the risk of disease worsening or death — a positive, but modest, result. Notably, overall survival results were not yet mature.
In Merck's KEYNOTE-407 study, results of which were disclosed Sunday, Keytruda plus carboplatin-paclitaxel or nab-paclitaxel drove a 4.6 month improvement in median overall survival. The risk of death was reduced by roughly 40% across patients with both high and low levels of PD-L1, as well as in those with no expression of the biomarker.
While the studies aren't directly comparable, Merck now appears to have set a bar that Roche will need to approximate in order to be commercially competitive.
Merck has already filed the data from Keynote-407 with regulators, hoping to secure an approval of a Keytruda plus chemo pairing in squamous NSCLC to add to its existing combo approval in non-squamous.
"Chemo combo in lung cancer clearly is setting the standard we are going to have to compare against," said Roy Baynes, senior vice president of clinical development at Merck Research Labs, in an interview.
KEYNOTE-042, on the other hand, proved that Keytruda monotherapy can deliver a survival benefit in a broad group of greater than 1% PD-L1 expressers — potentially positioning Merck to seek a label expansion. Currently, Keytruda monotherapy is only approved in patients who express 50% PD-L1 or higher.
Overall survival (OS) results from Keynote-042
|PD-L1 expression||Median OS, Keytruda||Median OS, chemotherapy||Hazard ratio|
|>50%||20 months||12.2 months||0.69|
|>20%||17.7 months||13 months||0.77|
|>1%||16.7 months||12.1 months||0.81|
SOURCE: Merck & Co
While the study met its objective in all patients with greater than 1% PD-L1, an exploratory analysis suggests that, for patients whose tumors expressed between 1% and 49%, the difference between Keytruda and chemo is much more slight.
Additionally, it still remains unclear whether high-expressing patients are better served with Keytruda monotherapy or Keytruda plus chemo.
Gilberto Lopes, study investigator and an oncologist at the Sylvester Comprehensive Cancer Center at the University of Miami, believes that choice will continue to be a matter of debate, but believes many doctors will favor the chemo combo.
The results from KEYNOTE-042 could also give physicians greater confidence to prescribe Merck's drug alone for those patients who might not be able to tolerate chemo's toxicity.
On safety, roughly 18% of patients given just Keytruda experienced a serious treatment-related adverse event, compared to 41% in the chemotherapy group.
Despite the strong results, Lopes noted that combinations too remain an imperfect treatment.
"Even with the combinations, the vast majority of patients are progressing and dying because of their cancer," Lopes said. "We do need to improve on the combinations."
To that end, Merck, Bristol-Myers and Roche are all pushing aggressively ahead with testing their respective PD-L1 inhibitors in a dizzying array of combinations. Both Bristol-Myers and Roche are scheduled to present more data on their drugs combined with chemo over the next two days of the ASCO meeting.
For now, Merck remains in the driver's seat in first-line NSCLC, fueled by Keytruda's combo and monotherpay wins.