Moving drugs into early-stage cancers is in vogue these days. Roche has just posted a trial win for its targeted lung cancer therapy Alecensa that should enable earlier use, while eliciting a sense of déjà vu from a study of AstraZeneca’s Tagrisso.
Alecensa reduced the risk of tumor recurrence or death by a whopping 76% over chemotherapy when used after surgery in patients with stage 1b to 3a, ALK-positive non-small cell lung cancer (NSCLC), according to phase 3 data presented at the European Society for Medical Oncology 2023 congress.
Investigators estimated that 88.7% of patients who took Alecensa remained alive without their disease returning after three years, compared with 54% for those in the chemo arm.
Charlie Fuchs, M.D., who leads oncology and hematology drug development at Roche and Genentech, described Alecensa’s disease-free survival showing as “unprecedented.” But whether doctors will quickly embrace the idea of adjuvant Alecensa remains to be seen.
Alecensa’s ALINA trial readout brings a sense of déjà vu from AstraZeneca’s ADAURA trial for Tagrisso in postsurgery patients with EGFR-mutated NSCLC back in 2020.
At that time, the AZ EGFR star cut the risk of disease recurrence or death by a massive 83% compared with placebo in the adjuvant setting in what the trial investigators called a “home run.”
Although the FDA quickly approved Tagrisso as an adjuvant therapy that same year, some doctors remained skeptical about the indication. The lack of clear evidence that using Tagrisso upfront in early-stage disease could extend patients’ lives, plus how well Tagrisso has performed as the standard of care for metastatic disease, caused their reservations.
Now, Alecensa could face the same risk of becoming a victim of its own success. The drug is currently the most popular ALK inhibitor as a front-line treatment for metastatic ALK-positive NSCLC. In the first nine months of 2023, Alecensa brought in CHF 1.1 billion sales, good for 9% growth at constant exchange rates.
In the phase 3 ALEX study that got Alecensa its first-line nod, the drug reduced the risk of death by 29% compared with Pfizer’s Xalkori after a long-term follow-up, although the number doesn’t bear statistical significance. After five years, 60% of patients who started treatment with Alecensa were still alive.
The overall survival data from ALINA remain “very immature” because so few patients have died, so “there’s just no value in even trying to conclude anything,” Fuchs said. Investigators are still following patients, but as the metastatic trial has shown, deaths could occur very slowly in ALK-positive NSCLC.
“I think that tomorrow morning I will discuss patient by patient if they wanted to receive the chemotherapy because there is an overall survival benefit,” Marina Garassino, M.D., a thoracic cancer expert at the University of Chicago, said during an ESMO press conference. “And I will also discuss [Alecensa] because we have to remember that we had a very short follow-up. We don’t have the overall survival yet, and there is also some toxicity.”
Fuchs made the case that doctors should use Alecensa early by pointing to the drug’s ability to prevent brain metastases. There, adjuvant Alecensa cut the risk of developing tumors in the central nervous system or death by 78%. And Garassino noted it’s possible that this brain metastases benefit will translate into extended overall survival in the future.
The ALINA trial is also different from ADAURA in that Alecensa was pitted against chemotherapy, while Tagrisso was evaluated against placebo.
Already, the doctors with whom Genentech has interacted have embraced Alecensa’s benefit “quite enthusiastically,” Fuchs said.
Without sharing any details, Fuchs said Roche is talking to regulators and is committed to getting adjuvant Alecensa approved across the globe as quickly as possible.
Meanwhile, Roche is evaluating using Alecensa both before and after surgery in a phase 2 trial.
The company also has its PD-L1 inhibitor Tecentriq approved as an adjuvant therapy in NSCLC based on trial data in patients who don’t harbor actionable mutations such as EGFR and ALK.
Historically, tumors with those mutations don’t respond well to PD-1/L1 inhibitors. But whether there’s an opportunity to add checkpoint inhibitors to Alecensa, Fuchs said, is an open question.