- A combination of two AstraZeneca immunotherapy drugs proved no better than standard chemotherapy in a Phase 3 study of patients with metastatic lung cancer, results disclosed Wednesday by the British pharma showed.
- The trial, called NEPTUNE, paired AstraZeneca's approved checkpoint inhibitor Imfinzi with its experimental drug tremelimumab, testing the two against platinum-based chemo in previously untreated patients. Participants given the combination lived no longer, however, than those who received chemo.
- It's a setback for AstraZeneca's efforts to broaden use of Imfinzi into metastatic non-small cell lung cancer, a large market currently dominated by Merck & Co.'s rival Keytruda. While Imfinzi is now a standard treatment in the adjuvant setting, negative results from NEPTUNE and an earlier trial called MYSTIC limit the drug's expansion.
AstraZeneca's miss in NEPTUNE comes about a month after mixed study results set back Bristol-Myers Squibb's chances of challenging Merck in first-line lung cancer.
While both companies have other trials yet to read out in the tumor type, the negative findings from NEPTUNE and the second part of Bristol-Myers Squibb's CheckMate-227 make Merck's position more secure. Estimates from Cowen put U.S. market share for Keytruda (pembrolizumab) in metastatic lung cancer at more than 60%, which has helped lift sales of the drug substantially.
A big difference is in the treatment strategies employed by the various companies. Merck has chosen to combine Keytruda with chemo alone, while Bristol-Myers and AstraZeneca have put together two immunotherapies along with chemo.
Results to date have borne out Merck's strategy, showing Keytruda plus chemo to significantly reduce the risk of death versus chemo alone.
Immunotherapy studies in first-line lung cancer
|CheckMate-227 (Part 1)||Opdivo + Yervoy vs. chemo||~1,700||OS benefit in PD-L1 positive pts.|
|CheckMate-227(Part 2)||Opdivo + chemo vs. chemo||~500||No OS benefit|
|NEPTUNE||Imfinzi + tremelimumab vs. chemo||955||No OS benefit|
|POSEIDON||Imfinzi + chemo or Imfinzi + tremelimumab + chemo vs. chemo||1,000||Results due in Q3|
|CheckMate-9LA||Opdivo + Yervoy + chemo vs. chemo||700||Results due early 2020|
SOURCE: Companies, clinicaltrials.gov, Evercore ISI
In NEPTUNE, AstraZeneca analyzed results from patients whose tumors featured particularly high levels of genetic mutations, a measurement known as tumor mutational burden. Among study participants with a TMB score of 20 or more, Imfinzi (durvalumab) plus tremelimumab did not improve overall survival versus chemotherapy.
AstraZeneca plans to submit fuller results for presentation at an upcoming medical meeting.
To date, the commercial success of Imfinzi stems almost entirely from data supporting its use in adjuvant treatment of lung cancer following chemoradiation.
In that setting, Imfinzi has stood alone, although Merck, Bristol-Myers and Roche also threaten. Cowen predicts Imfinzi's share of the adjuvant lung cancer market in the U.S. to slip from 100% in 2018 to about 70% by 2024. By contrast, for advanced disease, Imfinzi's share isn't predicted to rise above 10% over that time frame.
AstraZeneca can point to one metastatic success. In the less common small cell form of lung cancer, Imfinzi plus chemotherapy extended survival when compared to chemo alone, according to an early analysis of a study called CASPIAN.
Non-small cell lung cancer accounts for between 80% and 85% of all cases.
Imfinzi's more mixed clinical progress also stands in contrast to AstraZeneca's other cancer offerings, namely Lynparza (olaparib) and Tagrisso (osimertinib). Both drugs have carved out leading positions in ovarian cancer and EGFR-mutated lung cancer, respectively, helping AstraZeneca in its shift away from primary care drugs.