If approved, will US oncologists use Keytruda with
chemotherapy in first-line NSCLC?
From a strategic perspective, it was with some
significance that Merck & Co. recently announced the FDA has accepted its
supplementary new drug application for Keytruda to be used in combination with
chemotherapy for the treatment of first-line metastatic, non-squamous,
non-small-cell lung cancer regardless of PD-L1 expression (Stealing their
thunder? – Merck & Co. does it again).
Last year, Keytruda was approved as monotherapy for
treatment naïve NSCLC patients whose tumours express PD-L1 levels of 50 percent
or greater; a population estimated to account for approximately 25 percent of
the first-line market. Approval of Keytruda in combination with chemotherapy,
for the label Merck is seeking, would expand the addressable market to
approximately 80 percent to 85 percent of the treatment naïve population,
estimate analysts at BMO Capital Markets.
However, even assuming FDA approval is granted, will
oncologists use this combination with any enthusiasm?
Merck's application is based on a small, albeit
impressive, dataset from the Keynote-021 (Cohort G) study. A randomised Phase
II trial that enrolled 123 patients. Data were presented at last year's ESMO
congress, demonstrating an overall response rate (ORR) of 55 percent for the
Keytruda plus chemotherapy combination versus 29 percent for chemotherapy
alone, and a median progression-free survival benefit of 13 months for Keytruda
plus chemotherapy versus 8.9 months for chemotherapy.
Importantly, the two treatment arms demonstrated
comparable safety profiles and the combination of Keytruda plus chemotherapy
was shown to be particularly effective in PD-L1-negative patients, where it
demonstrated an ORR of 57 percent versus 13 percent for chemotherapy alone.
PD-L1 negative patients are estimated to account for approximately 25 percent
of the first-line NSCLC market and typically show minimal therapeutic response
to PD-(L)1 inhibitor monotherapy.
At six months, however, the overall survival (OS) rate
in both treatment arms was 92 percent. Although Merck has noted there was
extensive patient crossover in the trial; 52 percent of patients receiving
chemo-monotherapy crossed over to an anti-PD-(L)1 therapy, while no patients receiving
Keytruda plus chemotherapy did, these data will do little to allay concerns
among key opinion leaders that using PD-(L)1 inhibitor therapy and chemotherapy
in combination provides minimal or no long-term durable benefit and improvement
in OS. Until more data is available, many physicians may prefer to use
sequential, rather than concurrent use, of PD-(L)1 inhibitors and chemotherapy.
To better ascertain the mind-set of practising
oncologists ahead of potential approval for this combination in May, we are
asking US-based oncologists the following questions…
Are you based in an academic or community setting?
Academic
Community
The FDA has accepted a filing for Keytruda plus
chemotherapy for treatment of metastatic or advanced, non-squamous NSCLC
regardless of PD-L1 expression and with no EGFR/ALK tumour aberrations. Filing
is based on data from a 123-patient, randomised Phase II study showing a 55%
ORR for Keytruda/chemo versus 29% for chemo and a mPFS of 13 months for
Keytruda/chemo versus 8.9 months for chemo. Six-month OS was 92% for both arms;
52% of chemo-only patients crossed over into other arm. Safety profiles for
both arms were comparable.
Assuming approval of Keytruda/chemo in May, would you
consider using this combo in patients who you would otherwise consider treating
with chemotherapy?
No
Yes – very
infrequently
Yes – infrequently
Yes –
frequently
Yes – very frequently
Data shows improved response rate for Keytruda/chemo
to be greatest versus chemo only in PD-L1 negative patients; an ORR of 57% for
Keytruda/chemo versus 13% for chemo only. Taking into account that PD-1
inhibitor monotherapy tends to offer little benefit to these patients, and
assuming approval of Keytruda/chemo in May, would you consider using this combo
in PD-L1 negative patients?
No
Yes – very
infrequently
Yes – infrequently
Yes –
frequently
Yes – very frequently
Which of the following statements best describes your
current stance on the use of Keytruda/chemotherapy for the treatment of
first-line NSCLC patients based on the data submitted to FDA?
Very enthusiastic about this data and clinical profile
offered by the combination; will use if approved
Enthusiastic but need to see durability effect and OS
benefit before changing treatment practice/data provides insufficient evidence
to support use of concurrent pembro/chemo treatment instead of sequential use
Not enthusiastic – FDA should not approve this
combination on strength of data
Do you agree with the view that if subsequent data
show an OS benefit in favour of PD-1/chemo versus chemo alone, this combination
will prove highly popular with oncologists as it offers a cheaper combination
option versus immunotherapy plus immunotherapy combinations and physicians are
extremely familiar with the toxicity profile of chemotherapy?
No
Yes – agree somewhat
Yes – agree
Yes – agree completely
Results and related analysis will be published for
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