Physician Views: Practice-changing data in lung cancer at ESMO? – we're asking oncologists

Data from a number of potentially practice-changing clinical studies in non-small-cell lung cancer (NSCLC) were presented at the European Society of Medical Oncology (ESMO) congress in Madrid this weekend.

AstraZeneca took centre stage, with data for its PD-L1 inhibitor Imfinzi – in stage III unresectable NSCLC – and EGFR inhibitor Tagrisso – in first-line EGFRm-positive NSCLC – winning many plaudits (ESMO Spotlight: AstraZeneca delivers compelling riposte to MYSTIC setback with PACIFIC, FLAURA data).

Furthermore, Merck & Co. presented updated results from its Phase II Keynote-021 (Cohort G) study, which is assessing a combination of its PD-1 inhibitor Keytruda with chemotherapy versus chemotherapy alone in first-line metastatic NSCLC (ESMO Spotlight: Despite more positive data, Merck & Co. unable to fully shrug off chemo/combo uncertainties).

On the back of these data, we are snap-polling US and EU5-based oncologists to gauge their reaction. Specifically, we are asking them…  

The PACIFIC trial compared sequential treatment with the PD-L1 inhibitor durvalumab versus placebo in patients with locally advanced, unresectable stage III NSCLC who had not progressed following platinum-based chemotherapy concurrent with radiation therapy. It included 713 patients who were randomised 2:1 to receive durvalumab 10 mg/kg every two weeks or placebo for up to 12 months. The co-primary endpoints were progression-free survival (PFS) and overall survival. Results from a pre-planned interim analysis at 14.5 months were presented. The median PFS was 16.8 months in the durvalumab arm compared to 5.6 months with placebo, with a hazard ratio of 0.52.

How confident are you this is practice changing for the treatment of stage III NSCLC?

Not confident

Slightly confident

Moderately confident

Very confident

Extremely confident

Based on these data, would you consider using durvalumab, and/or another PD-1 or PD-L1 inhibitor, for the treatment of locally advanced, unresectable stage III NSCLC on an off-label basis?

Never

Rarely – only durvalumab

Rarely – durvalumab or alternative PD-(L)1

Sometimes – only durvalumab

Sometimes –  durvalumab or alternative PD-(L)1

Often – only durvalumab

Often –  durvalumab or alternative PD-(L)1

Always – only durvalumab

Always – durvalumab or alternative PD-(L)1

The Phase III FLAURA trial compared osimertinib to erlotinib or gefitinib as first-line therapy in EGFRm positive NSCLC. The primary endpoint was PFS. A total of 556 patients from Asia, Europe and North America were randomised 1:1 to treatment with osimertinib or standard of care.

Median PFS was 18.9 months with osimertinib versus 10.2 months for erlotinib/gefitinib, with a hazard ratio of 0.46. Benefit in PFS was consistent across all subgroups, including patients with and without brain metastases at the start of the study. Median duration of response was two-fold higher for patients treated with osimertinib (17.2 months) versus erlotinib/gefitinib (8.5 months). Overall response rate was 80% with osimertinib compared to 76% with erlotinib/gefitinib. Overall survival appeared to favour osimertinib with a hazard ratio of 0.63, although this was not statistically significant at the interim overall survival analysis. Incidence of grade 3 or higher toxicities was lower for osimertinib (34%) than the standard treatment (45%).

How confident are you that osimertinib should replace erlotinib/gefitinib as first-line treatment for EGFRm positive NSCLC?

Not confident

Slightly confident

Moderately confident

Very confident

Extremely confident

How important a role do you think mature overall survival data from FLAURA will play in driving utilisation of osimertinib in first-line patients? (assuming it is statistically significant in favour of osimertinib)

Not important – the PFS data are compelling enough

Slightly important

Moderately important

Very important

Extremely important – the PFS data are not compelling enough

The Phase I/II Keynote-021 (Cohort G) study evaluated the efficacy and safety of pembrolizumab in combination with pemetrexed and carboplatin compared with pemetrexed and carboplatin in 123 patients with metastatic, non-squamous, EGFR- and ALK-negative NSCLC in the first-line treatment setting.

With a median of 18.7 months of follow-up, 56.7% of patients in pembrolizumab combination arm responded to treatment compared to 31.7% in the pemetrexed/carboplatin arm, while the pembrolizumab combination reduced risk of disease progression or death by 46%. In addition, despite approximately 75% of patients in the pemetrexed/carboplatin arm crossing over to treatment with a PD-(L)1 inhibitor, a trend in improvement in overall survival continues to be seen for pembrolizumab + pemetrexed/carboplatin compared to pemetrexed/carboplatin alone – new hazard ratio of 0.59 versus 0.90 at 10.6 months follow up and 0.69 at 14.5 months follow up).

How confident are you this is practice changing for the treatment of metastatic, non-squamous NCSCL?

Not confident

Slightly confident

Moderately confident

Very confident

Extremely confident

Results and related analysis will shortly 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 Medefield 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.