Physician Views: Has Merck & Co. raised the stakes with its Keytruda/chemotherapy data in first-line NSCLC? – FirstWord is polling oncologists to find out

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).

See ESMO – the key players and how they performed and Physician Views Poll Results: Feedback from 130 oncologists sheds light on ESMO's Keytruda/Opdivo showdown

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?

Not impressive

Marginally impressive

Moderately impressive

Very impressive

Extremely impressive

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?

Completely disagree

Disagree

Somewhat disagree

Neither agree nor disagree

Somewhat agree

Agree

Completely agree

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)?

Not impressive

Marginally impressive

Moderately impressive

Very impressive

Extremely impressive

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)

Completely disagree

Disagree

Somewhat disagree

Neither agree nor disagree

Somewhat agree

Agree

Completely agree

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.

As always, FirstWord would very much like to receive your feedback and suggestions. Note: FirstWord Polls are powered by MedePolls, a fast-turnaround service to conduct instant polls of up to five questions with guaranteed samples that include physicians from dozens of specialties and over 100 markets. To conduct this poll with a different audience, or an entirely different poll, contact us at info@firstwordpharma.com

To read more Physician Views articles, click here.