Esmo 2018 – Recapping a wild weekend

Vast amounts of data were presented at the Esmo meeting over the weekend. Here is a roundup of Vantage’s analysis of the most crucial trials.

Successful trials abounded at the annual meeting of the European Society for Medical Oncology in Munich this weekend, with startlingly good results in ovarian, prostate and breast cancers, among others. 

But success in the clinic does not necessarily translate into a commercial advantage, either because the population in which the drug works is too small, or the benefit, though statistically significant, is not great enough to be meaningful.

The tone for the meeting was set on Friday with data on Clovis’s Rubraca showing a 44% response rate among BRCA-positive prostate cancer patients with the Parp inhibitor (Encouraging early prostate data fail to lift Clovis, October 19, 2018). 

If this response rate holds up in later cuts of the data, and Rubraca manages to show durable responses of around six months, Clovis is in with a chance of winning accelerated approval and getting the first Parp to market in prostate cancer. However other datasets presented at the conference spurred questions about the potential of this class outside of BRCA-positive patients. A historical trial of Lynparza in this setting that generated stronger response rates also raised investor concerns about Rubraca‘s potential here, so in the end Esmo did little for Clovis’s share price. 

Rubraca may be the Parp to watch in prostate cancer but the ovarian niche belongs to Astrazeneca and Merck’s Lynparza. Data from the Solo-1 trial in early-stage BRCA-positive patients were so good that Lynparza could come to be regarded as the standard of care in the first-line maintenance setting (Lynparza delivers a huge result in first-line ovarian cancer, October 21, 2018).  

Only a fifth of ovarian cancer patients have the BRCA mutation and while there are hopes that Lynparza could eventually come to be used more widely this expansion will take time.

Targeted

On Saturday data presented on alpelisib, the PI3K inhibitor under development by Novartis, showed impressive efficacy in breast cancer patients, though only those with the correct mutation (In breast cancer Novartis hopes to succeed where Roche failed, October 20, 2018). The drug has very high selectivity for PI3K alpha, and its chances of becoming a second-line therapy for HR-positive, Her2-negative breast cancer look good – if regulators are not put off by its side-effect of hyperglycaemia. 

And infigratinb, a selective FGFR1-3 kinase inhibitor belonging to Bridgebio, has shown early promise in bile duct cancer, giving an overall remission rate of 25% in 71 FGFR-positive patients (Bile duct cancer doctors herald the age of targeted therapy, October 21, 2018). If this promise is borne out in later studies Novartis’s decision to license the drug to Bridgebio for just $65m will come to look a poor one. 

Javelin hits the spot

The Javelin Renal 101 study read out yesterday, showing that Pfizer and Merck KGaA’s Bavencio plus Inlyta beat the first-line standard of care, Sutent, in first-line renal cancer. It showed a 39% reduction in risk of progression among PD-L1-positive patients and a 31% reduction in all comers (Front-line kidney showdown now features four players, October 21, 2018). This combination could soon pose competition for Exelixis’s Cabometyx and Bristol-Myers Squibb’s Opdivo plus Yervoy combo in the first-line setting.

Not all the data presented lived up to expectations, however. 

On Saturday, Roche’s Tecentriq had a trial success, but arguably only in the technical sense. The Impassion-130 study in triple-negative breast cancer showed a statistically significant benefit over placebo among all comers on progression-free survival. But this was judged not to be clinically meaningful, likely limiting the anti-PD-L1 Mab to patients positive for this ligand (Roche misses the bullseye in triple-negative breast cancer, October 20, 2018).

And a look at various early and mid-stage tumour microenvironment disruptors had a sting in the tail for Merck & Co, whose MK-1454 failed to impress either as monotherapy or in combination with Keytruda in patients with solid tumours or lymphomas. The US group’s Rig1 activator MK-4621 was also unable to show efficacy, but Roche’s RG7461 produced promising results in 43 melanoma patients (Merck & Co fails to Sting, October 20, 2018). 

Lastly, look out for Vantage’s coverage from today at Esmo, concerning Loxo Oncology’s battle with Roche and Keytruda’s hopes in first-line head and neck cancer

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