Two important oncology drugs for AstraZeneca have returned with trial wins in early-stage non-small cell lung cancer (NSCLC). For the immunotherapy Imfinzi, upcoming detailed data will likely feed into an increasingly fierce market competition.
Using AstraZeneca’s Imfinzi around surgery helped stave off worsening of disease in patients with resectable early-stage NSCLC in a phase 3 trial, the British drugmaker said Thursday. Imfinzi’s improvement on the event-free survival marker was “statistically significant and clinically meaningful,” the company noted.
AZ plans to share detailed data from the trial at an upcoming medical meeting.
The study, dubbed Aegean, tested whether adding Imfinzi to chemotherapy before surgery, followed by Imfinzi monotherapy after surgery, benefited patients with stage 2A to 3B NSCLC. In the control arm, the only active drug patients received was chemotherapy alone before surgery.
AZ’s Imfinzi win comes only days after Merck & Co.’s immuno-oncology leader Keytruda claimed its own event-free survival win in resectable early-stage NSCLC. In the Keynote-671 study, Keytruda was tested as a neoadjuvant therapy and as an adjuvant therapy around surgery.
With the dueling wins, doctors and analysts will surely compare data from Imfinzi’s Aegean and Keytruda’s Keynote-671 trials side by side. For now, patient survival data remain immature for both regimens.
Imfinzi has become a standard of care in unresectable stage 3 NSCLC, although its power against stage 4 metastatic tumors appears weaker than Keytruda’s. Additionally, Imfinzi just recently failed to top chemo in certain stage 4 NSCLC patients in the Pearl study.
Last June, AZ said Aegean had hit the other primary endpoint by showing Imfinzi’s combo with neoadjuvant chemotherapy before surgery was better than chemo alone at inducing a pathologic complete response.
Now, after Imfinzi hit its event-free survival goal, one question remains unanswered: How can one tease out the contribution of post-surgery adjuvant use of Imfinzi? In other words, do patients need additional adjuvant Imfinzi after receiving the medicine in the neoadjuvant setting?
Industry watchers might garner some clues from Bristol Myers Squibb’s CheckMate-816 trial, which last year won Opdivo a first-in-class FDA approval as a neoadjuvant therapy in early-stage NSCLC. There, Opdivo, used on top of neoadjuvant chemo, cut the risk of event-free survival by 37% over chemo alone in stage 1B to 3A NSCLC. If Aegean’s event-free survival comes below 37%, there will be some serious questions about using Imfinzi around surgery.
A more direct comparison could come from Bristol’s CheckMate-77T trial, which adopts a similar perioperative design for Opdivo both before and after surgery. Bristol expects the trial to report data in 2024. Roche is also moving toward a 2024 readout for Tecentriq’s perioperative NSCLC trial, IMpower030.
PD-1/L1 inhibitors have so far been approved for neoadjuvant and adjuvant NSCLC separately. Earlier this year, Keytruda followed Roche’s Tecentriq into adjuvant NSCLC. But Merck CEO Rob Davis recently tempered near-term sales expectations for the indication.
“This is a meaningful opportunity long-term, but it’s going to take us time to ramp as we work to change the (diagnosis) paradigm,” Davis said during the company’s fourth-quarter call.
Currently, doctors are more inclined to use immunotherapy before surgery versus after surgery. Compared with postsurgery use, presurgery treatment with PD-1/L1 involves shorter treatment time and fewer doses.
Compared with Aegean, the other early-stage NSCLC win AZ touted on Thursday could be less controversial. The company’s EGFR inhibitor Tagrisso significantly extended patients’ lives against placebo in the adjuvant treatment of 1B to 3A EGFR-mutated NSCLC after complete tumor resection. The result came from the phase 3 Adaura trial.
Tagrisso in late 2020 won FDA approval for adjuvant treatment of NSCLC based on data from the same trial showing the targeted therapy slashed the risk of disease recurrence or death by a whopping 83%.
“[T]hese exciting overall survival results validate adjuvant Tagrisso as the standard of care in this setting and reinforce the importance of early diagnosis and testing for EGFR mutation in lung cancer,” AZ’s oncology R&D head, Susan Galbraith, said in a statement.
Meanwhile, AZ is trying to push Tagrisso into even earlier treatment of NSCLC. The Adaura2 trial is testing adjuvant Tagrisso in stage 1A2 and 1A3 cancer, and the NeoAdaura study is evaluating Tagrisso as a neoadjuvant therapy. Separately, AZ also expects data from the phase 3 Laura trial for Tagrisso in unresectable stage 3 NSLC in the second half of 2023.