Roche’s Tecentriq triplet versus Keytruda + chemotherapy: an Uphill Struggle?

17th December 2018 (Last Updated August 9th, 2019 09:35)

On December 7 Roche announced the FDA approval of its triplet of programmed death-ligand 1 (PD-L1) inhibitor Tecentriq (atezolizumab) + vascular endothelial growth factor (VEGF) inhibitor Avastin (bevacizumab) + chemotherapy (paclitaxel + carboplatin) in the highly prized indication of untreated non-squamous non-small cell lung cancer (NSCLC).

Roche’s Tecentriq triplet versus Keytruda + chemotherapy: an Uphill Struggle?

On December 7 Roche announced the FDA approval of its triplet of programmed death-ligand 1 (PD-L1) inhibitor Tecentriq (atezolizumab) + vascular endothelial growth factor (VEGF) inhibitor Avastin (bevacizumab) + chemotherapy (paclitaxel + carboplatin) in the highly prized indication of untreated non-squamous non-small cell lung cancer (NSCLC). This approval means that Roche may be the first company to present any real threat to Merck’s Keytruda (pembrolizumab) + chemotherapy combination, which was FDA-approved for untreated non-squamous NSCLC in August 2018, although it still faces significant challenges in this indication.

The Keytruda combination approval was supported by astonishing survival data presented at the American Association for Cancer Research (AACR) 2018 conference, demonstrating that Keytruda + chemotherapy halved the chance of death versus chemotherapy alone in Phase III KEYNOTE-189 study. In comparison, Roche’s triplet reduced the risk of death by around a quarter in its pivotal Phase III IMpower 150 study. Both combinations have demonstrated significant benefits across PD-L1 expression subgroups, therefore their target populations overlap completely and Roche will need to differentiate its triplet if it wants to gain any market share. Given Merck’s head start and impressive efficacy, the battle with Merck’s doublet may be lost. Roche, however, can focus its efforts on differentiating its regimen against upcoming entrants, such as touting its efficacy across PD-L1 subtypes, or emphasising its promising survival data and the availability of longer-term follow-up.

Roche’s triple therapy may also face scepticism both from payers and physicians as it comes in second to market, as a triple regimen may mean additional toxicity; although no safety concerns have been raised with the triplet so far, the addition of a targeted agent to an immuno-oncology + chemotherapy combination could be associated with compound toxicity, as well as a significantly higher cost than Merck’s doublet. Roche will have to leverage a lower price point for its in-house combination to encourage payer and physician uptake. However, given the Keytruda doublet’s impressive efficacy, this discount may have to be high to secure any sales of the triplet regimen. The Roche combination is also a late entrant to the market, given that the Keytruda combination has a significant head-start. Merck may benefit from increased physician familiarity and good perceptions of Keytruda + chemotherapy’s efficacy and safety in this setting, potentially impacting sales of any future entrants, not just Roche’s combination.

Although Roche’s triplet therapy faces many challenges in making headway against Merck’s combination, the setting of first-line NSCLC remains one of the most profitable markets for immuno-oncology drugs, and its second-place position leaves Roche ahead of key potential competitors such as Bristol-Myers Squibb and AstraZeneca.