Roche yesterday came out fighting for a slice of the first-line metastatic lung cancer market in what is becoming an increasingly complex battle between several anti-PD-(L)1 antibodies.
This was despite the unexpected early positive readout of Merck & Co’s Keynote-189 trial on the one hand, and what were seen as underwhelming survival data from Roche’s own Impower-150 study on the other. The Swiss group refused to accept that it was falling behind, and insisted that Avastin would play a part in a Tecentriq/chemo combo.
Still, Merck’s Keytruda has already beaten Tecentriq to this market, securing accelerated approval based on the uncontrolled Keynote-021G trial, and Keynote-189 data should formalise this green light. Avastin plays a separate but also important role for Roche.
An update of the Impower-150 readout at December’s Esmo-IO congress suggested that Avastin on top of Tecentriq plus dual chemo yielded a minimal improvement in survival – and added toxicity. “It is not yet clear that Avastin will play a significant role as part of a more expensive, toxic cocktail,” wrote Bernstein analysts.
At Roche’s full-year financials conference yesterday the group said that for patients “comfortable” with Avastin adding Tecentriq could be an option, and insisted to EP Vantage that Avastin toxicities were relatively transient. The big question is why Avastin plus chemo should not just be replaced with Tecentriq plus chemo.
Avastin, a key franchise for Roche, has already been hit by immuno-oncology: 2017 sales fell 2% to CHF6.7bn ($7.2bn). Even worse, it looks to face biosimilars competition starting in 2020, so bundling it with Tecentriq in first-line NSCLC could be strategically important.
In the game
Of course, Tecentriq itself is still in play in first-line NSCLC: Impower-150 is a three-arm study, which showed a clear benefit for Tecentriq, Avastin and chemo over Avastin and chemo alone. “In no way do I think the battle is won in the first-line setting,” Roche’s pharma chief, Daniel O’Day, told an analyst breakout session yesterday.
However, doubts about Avastin arose at the Esmo-IO update, which quietly unveiled the Tecentriq plus chemo arm. The still immature data showed overall survival for Tecentriq plus chemo to be running at 17.9 months – just 1.3 months less than the Tecentriq/Avastin/chemo combo (Esmo I-O – Roche’s lung cancer data fail to Impower, December 7, 2017).
Though Impower-150 is not powered for such analysis, the suggestion is that the latter combo’s benefit is driven not by Avastin but by Tecentriq.
|What we know about Impower-150 so far (NCT02366143)|
|Arm B||Arm C||Arm A|
|(Tecentriq + Avastin + chemo)||(Avastin + chemo)||(Tecentriq + chemo)|
|Median progression-free survival||8.3 months||6.8 months*||6.8 months|
|Stats for B vs C||HR 0.62, p<0.0001||–|
|Stats for A vs C**||–||HR 0.94, not stat sig|
|Median overall survival||19.2 months||14.4 months||17.9 months|
|Stats for B vs C||HR 0.78, p=0.0262||–|
|Stats for A vs C**||–||HR 0.88, not stat sig|
|Note: *reported as 6.3 by the Esmo-IO discussant, who Roche clarified was using an older, incorrect version of the PFS figure; **formal statistical analysis of arm A vs arm C has not yet been carried out, and Impower-150 has not been powered to detect a difference between these two arms.|
Full Impower-150 survival readout is due in the first half, and Mr O’Day whetted the market's appetite by revealing that this should come “in the relatively near term, so it shouldn’t be too much longer”.
The first half is also when Merck & Co will unveil full data from Keynote-189, a Keytruda/chemo combo study already toplined as positive (Surprise! Keytruda scores early lung cancer win, January 16, 2018). And Astrazeneca will reveal survival data from Mystic, testing Imfinzi as monotherapy and combined with tremelimumab, though given failure at the first analysis this is a long shot.
The Keytruda/chemo combo already has US accelerated approval in first-line NSCLC, though “many physicians we hear from are waiting to see the confirmatory data [from Keynote-189] before they use that extensively”, said Mr O’Day.
He also stressed the importance to Roche of Impower-132, a trial of Tecentriq and a triple chemo regimen without Avastin that he said was “most equivalent to Keynote-189”, due to read out before the half-year.
Not giving up
Neither is Astra giving up on Imfinzi, the likely failure of Mystic notwithstanding. Reporting its full-year numbers today the group said it was important to wait until full results of Keynote-189 were known.
Astra does have one ace up its sleeve: Imfinzi’s positive result in Pacific, a study of stage III, non-metastatic NSCLC patients who are at present poorly served. The data have been submitted to regulators, and US approval is expected in the first half.
This indication is important, as it could affect the chances of rival IO agents, which are targeting the later, stage IV metastatic use, as well as establishing Imfinzi as a creditable drug with lung cancer doctors. “We are first, and will be by ourselves for quite some time,” said Astra’s chief executive, Pascal Soriot, of the Pacific setting.
He also pointed to uses beyond NSCLC, such as the highly intractable small-cell lung cancer, in which Imfinzi with or without tremelimumab is in the Caspian trial. For its part, Roche also highlighted Tecentriq’s Impower-133 study, which it said gave it a chance to be first to market in SCLC.
“And we have nothing to apologise for over Impower-150 data,” stressed Mr O’Day.