KANTAR HEALTH BLOG

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Calquence ELEVATE data continues to push field to new heights in CLL.

by Megan Epperson | Dec 9, 2019

This is Megan from Kantar here at ASH2019 in beautiful Orlando!

In one of the opening sessions at ASH on Saturday, data from the Phase 3 ELEVATE trial evaluating Calquence (acalabrutinib) alone or in combination with Gazyva versus Gazyva plus chlorambucil was presented, finally giving us a look at all of the details from the trial that supported the filing and recent accelerated approval for in treatment-naïve CLL for unfit patients.

As we have seen from early reports of the ELEVATE data and the recent approval, the primary endpoint of PFS was met with flying colors, with the Calquence + Gazyva combination boasting a hazard ratio of 0.1, the highest we’ve yet seen from the recently approved regimens in this setting which also include Venclexta or Imbruvica in combination with Gazyva for the same unfit patient population. Calquence alone also improved PFS, and both the combination and the monotherapy showed this benefit across patient subgroups including del17p. The data reported for additional endpoints like OS, and ORR, also showed a strong benefit and highly favored either the Calquence + Gazyva combo or the monotherapy.

With data this impressive, you would think this could be the clear new standard of care in this setting. However, the treatment-naïve setting, and particularly the unfit patient population, has been a hotbed of activity in the last few years, with multiple approvals and pivotal trials still ongoing.

There are currently three recent approvals in this setting featuring the same combination partner, Venclexta, Imbruvica, and now Calquence all in combination with Gazyva vs Gazyva plus chlor, and data from all three have been strong.

So how will this battle play out? This was, in fact, the first question from an audience member immediately following the presentation: “A patient comes in to your office…how do you treat them? Which combo do you use?”. An audible chuckle from both panel and audience made it clear this was the question at the top of everyone’s minds. There is no one answer, and the choice won’t be made on the PFS hazard ratios alone. While Calquence + Gazyva wins on PFS hazard ratio, and has a slightly higher ORR than the others, the Venclexta + Gazyva combo showed strong improvement in these measures as well, and additionally boasts a nearly 50% CR rate…much higher than has been reported for the Imbruvica (19%) or the Calquence (13%) combination. 

The Imbruvica hazard ratio for PFS was also impressive at 0.2, and with the monotherapy being a highly utilized standard of care across both fit and unfit patient types regardless of del17p status, it has the home field advantage in terms of entrenchment and familiarity, making it a tough competitor to unseat, even with exemplary data.

The AE profiles of each combo are generally tolerable, with the discontinuation rate due to adverse events being the highest for the Venclexta combo at 16%, Imbruvica and Calquence combos both hovering near 10%.

The dosing for both Calquence and Imbruvica combos with Gazyva is continuous dosing until progression or toxicity, while the Venclexta combo offers a limited dose of 12 cycles, which could be a factor in patient preference.

What does this all mean for impact to standard of care and adoption of these agents? Physicians will now have the option of Calquence monotherapy in addition to current standard of care Imbruvica monotherapy if adding Gazyva is not an appropriate strategy for that patient  Though certainly, in the near future, many physicians could switch to some kind of combination strategy of Imbruvica, Venclexta, or Calquence in combination with Gazyva for some portion of their unfit patients in the first-line…but as to how quickly and completely each will be adopted, the devil is in the details, and the choice will likely be very physician- and patient-dependent. For now, we wait for more time and experience with this expanding physician toolkit and keep our eyes on the brewing competitive landscape.

ELEVATE VLOG 120719

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