Physician Views: Post-ESMO, FirstWord is polling oncologists with five key questions about future PD-(L)1 inhibitor use in first/second-line NSCLC

Presentation of data from the Keynote-024 and Checkmate-026 studies at the European Society of Medical Oncology (ESMO) annual meeting this weekend has shed more light on how PD-1 inhibitor monotherapies will be used to treat first-line non-small-cell lung cancer (NSCLC) patients.

For further analysis of the key stories from ESMO see ESMO – the key players and how they performed and ESMO – key questions raised by new PD-1 inhibitor datasets

In Keynote-024, Merck & Co. presented solid data for Keytruda in first-line patients whose tumours had >50 percent PD-L1 expression, including median progression-free survival of 10.3 months versus 6 months for chemotherapy (hazard ratio of 50 percent). It is estimated that this population accounts for approximately 25 percent of all newly diagnosed NSCLC patients and FDA approval in this indication is expected by the end of 2016.

In CheckMate-026, which assessed a broader population of first-line patients whose tumours had >1 percent PD-L1 expression, Bristol-Myers Squibb's Opdivo demonstrated median progression-free survival of 4.2 months versus 5.9 months for chemotherapy. Surprisingly, given the broadly held view that Keytruda and Opdivo are very similar products, Opdivo also provided no meaningful benefit in tumour progression or survival rates versus chemotherapy in patients with >50 percent PD-L1 expression.

Until PD-1 combination studies read out – beginning next year – it appears that Merck will enjoy a monopoly in the first-line setting, albeit mainly in higher-expressing PD-L1 patients. However, results from an earlier Physician Views poll, fielded in response to top-line results from CheckMate-026 in August, indicate that first-line Keytruda use could 'bleed' into patients whose tumours express <50 percent PD-L1 and suggest a positive 'halo' effect for Merck's drug in second-line patients (where Opdivo, to date, has dominated the market) – Physician Views Poll Results: Bristol-Myers Squibb's Opdivo setback could have profound implications for Merck & Co.'s Keytruda.

Furthermore, data presented by Roche at ESMO for its PD-L1 inhibitor Tecentriq highlights the emergence of an additional competitive threat in second-line patients; as predicted when results from the OAK study were top-lined last month (ViewPoints: Roche throws curveball with Tecentriq data).

In response to the presentation of data from Keynote-024, CheckMate-026 and the OAK studies, FirstWord is asking US and EU5-based oncologists the following questions in our latest Physician Views poll…

Full results from the Keynote-024 study of Keytruda (pembrolizumab) in first-line NSCLC (patients with >50% PD-L1 expression) demonstrate median progression-free survival of 10.3 months for Keytruda versus 6 months for chemotherapy (hazard ratio of 50%). Median overall survival data is not yet mature, but at six months 80.2% of Keytruda patients were alive versus 72.2% of chemotherapy patients (hazard ratio of 60%). Twenty-seven (27) percent of Keytruda patients experienced grade 3-5 side-effects versus 53% of chemotherapy patients. 

Once available, how quickly do you expect Keytruda to be adopted as the standard-of-care therapy in first-line NSCLC patients whose tumours express PD-L1 >50%?

Not adopted

Slowly

Moderately

Quickly

Very quickly

Full results from the CheckMate-026 study show that in first-line NSCLC patients with >1% PD-L1 expression, Opdivo (nivolumab) demonstrated median progression-free survival of 4.2 months versus 5.9 months for chemotherapy. Opdivo also provided no meaningful benefit in tumour progression or survival rates versus chemotherapy in patients with >50% PD-L1 expression.

Do these data change your current perception of Opdivo's clinical profile?

Unchanged (i.e. study design to blame)

Marginally worse

Moderately worse

Significantly worse

Substantially worse

Taking data from the Keynote-024 and CheckMate-026 studies into account, once approved would you expect to use Keytruda monotherapy in first-line patients with <50% PD-L1 expression?

No

Yes – marginal use

Yes – moderate use

Yes – significant use

Yes – very significant use

Given the respective clinical data for Keytruda and Opdivo in first-line NSCLC patients, do you expect this to have a positive impact on your use of Keytruda in second-line patients?

No

Yes – marginally

Yes – moderately

Yes – significantly

Yes – very significantly

In the Phase III OAK study, Tecentriq (atezolizumab) demonstrated median overall survival (OS) of 13.8 months versus 9.6 months for chemotherapy (hazard ratio of 73%) in second- and third-line NSCLC patients regardless of PD-L1 expression. In patients with >1% PD-L1 expression, Tecentriq demonstrated a median OS of 15.7 months versus 10.3 months for chemotherapy (HR of 74%) and in patients with <1% PD-L1 expression, Tecentriq demonstrated a median OS of 12.6 months versus 8.9 months for chemotherapy (HR of 75%). Patients who already had a strong immune response are reported to have fared even better on the drug, with these subjects living a median of more than 20 months, compared with 8.9 months for chemotherapy.

Taking into account that Tecentriq is also dosed once every three weeks (versus every two weeks for Opdivo) how much market share would you expect it to gain at the expense of Opdivo in second-line patients?

None

Marginal share

Moderate share

Significant share

Very significant share

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.

Reference Articles