The annual European Society of Medical Oncology (ESMO) congress takes place in Madrid on September 8-12 and this year (like last) is poised to rival the American Society of Clinical Oncology (ASCO) meeting for important clinical presentations. FirstWord will be in attendance and we preview key data readouts below…
Merck's Keytruda plus chemotherapy for non-small-cell lung cancer – Keynote-021 (Cohort G) trial
Merck has already secured accelerated US approval for the combination of Keytruda and Alimta in treatment naïve non-small-cell lung cancer patients based on positive PFS data from Keynote-021 and has also filed this combination with EU regulators on the basis of this study. Updated results presented at ASCO in June showed a trend towards overall survival (OS) benefit for the Keytruda/chemo arm (versus chemo monotherapy) and presentation of the Keynote-021 data on September 8 could enhance confidence ahead of the read out from Merck's larger Phase III trial later in 2017.
AstraZeneca's Imfinzi (durvalumab) for locally advanced (Stage III) unresectable non-small-cell lung cancer – PACIFIC trial
AstraZeneca confirmed in May that Imfinzi had met its primary progression-free survival (PFS) endpoint and approval could confer meaningful commercial opportunity for the company; with immuno-oncology front-runners Bristol-Myers Squibb and Merck & Co. yet to initiate pivotal-stage trials in this setting (ViewPoints: AstraZeneca becomes a trend setter in immuno-oncology). Details of the abstract will be released on September 9 when results from PACIFIC are presented, with AstraZeneca describing the data as "potentially transformative."
AstraZeneca's Tagrisso for advanced EGFRm non-small-cell lung cancer – FLAURA trial
AstraZeneca has confirmed that results from FLAURA will be presented at ESMO's presidential symposia on September 9. The company recently announced that Tagrisso demonstrated a "statistically significant and clinically meaningful progression-free survival benefit," over current standard of care as first-line therapy in previously untreated EGFRm non-small-cell lung cancer patients. Investors will be watching closely to see whether AstraZeneca's definition of a "clinically meaningful" benefit will determine that Tagrisso is quickly adopted as a first-line therapy, particularly in light of the company's recent MYSTIC setback.
Incyte and Merck's epacadostat plus Keytruda for melanoma – ECHO-202 trial
In an abstract released earlier this week, data from ECHO-202 showed median PFS of 12.4 months for all treatment-naïve patients treated who received the combination of Incyte's IDO inhibitor epacadostat and Merck's PD-1 inhibitor Keytruda. This would appear to compare favourably with the median PFS of 11.7 months for Bristol-Myers Squibb's combination of Opdivo and Yervoy, given that the epacadostat/Keytruda pairing is more tolerable. Following conversation with Incyte management, analysts at Barclays said results presented from ECHO-202 on September 9 will include new data, but results are unlikely to be significantly different. Analysts, nevertheless, appear impressed ahead of Phase III data – ViewPoints: More of the same at Incyte makes for a rousing success
Eli Lilly's abemaciclib for HR+/HER2- breast cancer – MONARCH 3 trial
Data from MONARCH 3 should provide the best comparison to date to Pfizer and Novartis' already approved CDK 4/6 inhibitors Ibrance and Kisqali (Physician Views: Assessing oncologists' pre-launch expectations for Novartis' Kisqali), with Eli Lilly maintaining that abemaciclib could demonstrate meaningful differentiation thanks to its more targeted mechanism of action and continuous-dosing schedule. With investor expectations modest at present, however, analysts at Barclays suggest that abemaciclib needs to demonstrate a hazard ratio of between 0.50 and 0.60, and diminishing rates of diarrhoea after the initial cycle of treatment, if confidence in its competitive profile is to increase. Featuring at the ESMO presidential symposium, data from MONARCH 3 will be released shortly ahead of presentation on September 10.
Clovis Oncology's Rubraca for ovarian cancer – ARIEL3 trial / Tesaro's Zejula for ovarian cancer – NOVA trial / Tesaro's Zejula and Merck's Keytruda in ovarian and triple-negative breast cancer – TOPACIO trial
With the FDA recently expanding approval of AstraZeneca's Lynparza to include maintenance treatment of ovarian cancer patients irrespective of BRCA mutation status, it looks like the FDA considers each of the marketed PARP inhibitors to be more similar than different – ViewPoints: New Lynparza label codifies PARPs as commodity to Tesaro’s chagrin.
If this emphasises the role of marketing in driving commercial success, then AstraZeneca's recent deal with Merck may prove a critical development where smaller competitors Clovis and Tesaro are concerned (KOL Views Results: Marketing departments may decide brewing battle of the PARPs in ovarian cancer, says leading oncologist). Both companies will present data from their registration-supporting maintenance treatment studies at ESMO, but the most intriguing data will likely concern the TOPACIO study, which is assessing combination use of Keytruda with Zejula in both ovarian and triple-negative breast cancer. These data could provide clues for where the AstraZeneca/Merck collaboration will move next, while Tesaro is developing its own PD-1 inhibitor for future combinations.
Merck's Keytruda in bladder cancer – Keynote-045 trial / Merck's Keytruda in gastric cancer – Keynote-059 trial
In May, Merck's Keytruda became the fifth PD-(L)1 inhibitor to be approved by the FDA for the treatment of bladder cancer (in both first- and second-line patients), but is the only treatment in class to have yet demonstrated an OS benefit in second-line patients. Data from the Keynote-045 trial, which supported approval in this setting, will be presented at ESMO on September 10 and have taken on greater significance with Roche's Tecentriq having failed to meet its OS endpoint. It will also provide a benchmark for Eli Lilly's Cyramza, which has delivered positive PFS data and is due to readout OS results next year – Physician Views Poll Results: Keytruda the biggest threat to Tecentriq in bladder cancer market, say oncologists.
Ahead of a scheduled PDUFA date of September 22 for the treatment of gastric cancer, data from the supporting Keynote-059 trial will be presented on September 8
Exelixis and Ipsen's Cabometyx in renal cell carcinoma – CABOSUN trial / Bristol-Myers Squibb's Opdivo plus Yervoy in renal cell carcinoma – CheckMate-214 trial
Data from the CABOSUN trial are being used to support a regulatory filing for Cabometyx in first-line renal cell carcinoma patients and Exelixis and Ipsen could potentially take advantage of Bristol-Myers Squibb's Opdivo/Yervoy failing to recently show a PFS benefit. That said, the CheckMate-214 study may subsequently demonstrate an OS benefit (updated results will be presented on September 10), which could determine possible future use of Cabometyx in first-line patients; particularly as the control arm in CABOSUN continues to attract some scrutiny – ViewPoints: Exelixis looks to seize on Bristol-Myers Squibb's uncertainty in renal cell carcinoma, but faces questions of its own
Merck's Keytruda in head and neck cancer – Keynote-040 trial
Merck has had a pretty good run of form in avoiding clinical setbacks with Keytruda, but succumbed to an unexpected bump in the road in July, when the PD-1 inhibitor just failed to miss its OS endpoint in the Keynote-040 trial assessing use versus chemotherapy in recurrent and metastatic head and neck cancer. The FDA is not expected to revoke accelerated approval for Keytruda in this setting and full data from the '040 study – to be presented on September 11 – will provide a clearer indication as to why – ViewPoints: Keytruda likely protected by anti-PD-(L)1 slipstream despite miss in HNSCC
Roche's Alecensa in ALK positive non-small-cell lung cancer – ALEX trial
While offering little in the way of surprise, new data from Roche's ALEX trial – studying Alecensa versus Xalkori in first-line ALK-positive non-small-cell lung cancer – will no doubt pack a punch given the magnitude of benefit shown in previously released results – Physician Views Poll Results: Oncologists offer more evidence that Roche's Alecensa has rewritten the rules in ALK-positive lung cancer
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