Immune checkpoint inhibitors (ICIs) have transformed the treatment of late-stage non-small cell lung cancer (NSCLC). Patients with resectable early-stage (Stage II–IIIa) NSCLC are typically treated by surgery, sometimes followed by adjuvant treatment with chemoradiotherapy, but no ICI had received marketing authorisation in this setting. Now following surgery, US patients with PD-L1 expression on ≥ 1% of tumour cells can be treated with Roche’s Tecentriq (atezolizumab), following a US Food and Drug Administration (FDA) approval based on interim results from the Phase III IMpower010 trial.
The trial’s primary endpoint was disease-free survival (DFS). The evaluable population included 476 patients who were randomised to receive Tecentriq or best supportive care as the control group. In the Tecentriq arm, median DFS was not reached, compared to a DFS of 35.3 months in the control arm (hazard ratio [HR]: 0.66). A subgroup analysis of patients expressing PD-L1 on more than 50% of tumour cells highlighted a DFS difference at a more impressive HR of 0.43.
Previous safety data presented at a satellite American Society of Clinical Oncology meeting showed that Grade 3/4 events occurred in 21.8% of patients receiving Tecentriq versus 11.5% in the control arm. The results of this study suggest that the more than 50% PD-L1 group derives the most benefit from adjuvant Tecentriq, which will undoubtedly affect physicians’ decision to prescribe Tecentriq in patients with PD-L1 expression of 1–50%. The long-term side effects from adjuvant treatment are not well appreciated yet, and more research into cancer-unrelated deaths should follow.
GlobalData believes that the adoption of Tecentriq in the adjuvant setting will be set back by the absence of overall survival (OS) data. The most clinical practice-changing trial in an NSCLC adjuvant setting so far, the Phase III ADAURA trial for the adjuvant use of AstraZeneca’s Tagrisso (Osimertinib), overcame the absence of OS data by showing a stunning DFS difference, at an HR of 0.17, resulting in reduced risk of disease recurrence or death by 83%. Even with such stellar data, several key opinion leaders (KOLs) have been vocal about the risk of adopting the ADAURA regimen without long-term OS readouts.
After fierce competition in the advanced/metastatic disease setting for ICIs, which has largely resulted in Merck & Co’s Keytruda (pembrolizumab) being declared as the winner, many companies are using the adjuvant setting as the next logical step in their ICI’s lifecycle. These include AstraZeneca’s Imfinzi (durvalumab), as well as Tecentriq and Keytruda. GlobalData forecasts the adjuvant-eligible population for NSCLC to include up to 55,000 patients in the US this year, of which up to 30% may eventually be assigned to any adjuvant ICI.
While Tecentriq should initially capture a small share of that market, long-term competition by Keytruda and Imfinzi is expected to be significant. In the absence of a head-to-head comparison, Keytruda will likely be favoured due to established physician preference.