The key focus at this year's European Society of Medical Oncology (ESMO) meeting (October 7-11) was presentation of data from the Keynote-024 and CheckMate-026 studies, assessing Merck & Co.'s Keytruda and Bristol-Myers Squibb's Opdivo, respectively, as first-line monotherapies for the treatment of non-small-cell lung cancer (NSCLC).
On the strength of these data, Merck looks poised to enjoy a considerable head-start in the first-line PD-1 monotherapy market. This sharpens focus on the development of combination regimens for the treatment of first-line NSCLC patients, which over time could replace PD-1 monotherapies.
Bristol-Myers Squibb and AstraZeneca are prioritising the development of PD-(L)1/CTLA-4 inhibitor combinations (Opdivo plus Yervoy and durvalumab plus tremelimumab, respectively), while Merck and Roche are prioritising PD-(L)1/chemotherapy combinations.
At ESMO, Merck also presented data from its Keynote-021 study, which is assessing Keytruda/chemotherapy versus chemotherapy alone in previously untreated advanced non-squamous NSCLC regardless of PD-L1 expression level. The data are preliminary and incomplete, and durability of effect needs to be shown in Phase III studies, but results from Keynote-021 nevertheless look impressive and on par with data presented for Bristol-Myers Squibb's Opdivo/Yervoy combination.
Our latest Physician Views poll seeks feedback from practicing oncologists (based in the US and EU5) on the Keynote-021 data presented at ESMO. Specifically we are asking them…
Keytruda plus chemotherapy demonstrated an overall response rate of 55% versus 29% for chemotherapy and median progression-free survival (mPFS) of 13 months (Keytruda/chemotherapy) versus 8.9 months (chemotherapy). Ten percent of patients receiving Keytruda plus chemotherapy discontinued therapy due to treatment-related adverse events versus 13% for chemotherapy alone, while 39% of Keytruda/chemotherapy patients and 26% of chemotherapy patients experienced Grade 3-5 adverse events. Six-month survival rate was 92% for both arms, but there was extensive patient censoring and crossover.
How impressive do you consider these data?
An overall response rate (ORR) of 55% for Keytruda plus chemotherapy compares to an ORR of 39% for the combination of Opdivo plus Yervoy – based on data from the Checkmate-012 study – while a mPFS of 13 months for Keytruda plus chemotherapy compares to a mPFS of 3.9 months for Opdivo/Yervoy. The Grade 3-5 adverse event rate was 39% for Keytruda/chemotherapy versus 33% for Opdivo/Yervoy. Based on these available data do you agree with the view that PD-1/chemotherapy combinations are 'competitive' with PD-1/CTLA-4 combinations?
Neither agree nor disagree
Overall response rate for Keytruda plus chemotherapy differed by PD-L1 status.
In PD-L1-negative (<1%) patients, Keytruda/chemo demonstrated an ORR of 57% versus 13% for chemotherapy and 0% for Opdivo/Yervoy. In PD-L1-positive (>1%) patients, it was 54% for Keytruda/chemotherapy versus 38% for chemotherapy and 57% for Opdivo/Yervoy. In PD-L1-positive patients (1-49%), it was 26% for Keytruda/chemotherapy versus 39% for chemotherapy and 44% for Opdivo/Yervoy. In PD-L1 high expressers (>50%), it was 80% for Keytruda/chemotherapy versus 35% for chemotherapy and 86% for Opdivo/Yervoy.
How impressive do you consider the data for Keytruda plus chemotherapy in PD-L1-negative patients (with a view to this being a viable opportunity for Keytruda/chemotherapy if subsequent data is supportive)?
Considering these same response rate data – as stratified by PD-L1 status – do you agree with the view that future PD-1 combination use in first-line NSCLC will be heavily segmented? (i.e. neither PD-1/chemotherapy or PD-1/CTLA-4 combinations will dominate across the board)
Neither agree nor disagree
Have these new data from the Keynote-021 study (assessing the combination of Keytruda and chemotherapy) provided you additional conviction that chemotherapy will retain a future place in the treatment of first-line NSCLC?
No – and I was already unconvinced that chemotherapy will retain a place
No – but I was already moderately confident that chemotherapy would retain a place
No – but I was already very confident that chemotherapy would retain a place
Yes – marginally
Yes – moderately
Yes – significant
Yes – very significantly
Results and related analysis will be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here.
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