introduction of anti-PD-1 or anti-PD-L1 antibodies.
The evaluation of PD-L1 expression in tumour cell
sand/or inflammatory cells is the most widely
used predictive assay. However PD-L1 has a
heterogeneous expression pattern and different
antibodies are available for this assessment. There
are different evaluation schemes in different
tumours to assess PD-L1 positivity and match the
patient to the therapy. Moreover, it is well known
that some patients having tumours with high
PD-L1 expression might show hyper-progression
during anti-PD1–PD-L1 therapy. To overcome
these issues, a potential biomarker has been
introduced recently: namely, the tumour
mutation burden (TMB).
Patient-specific neoantigens that develop as
a result of somatic mutations can induce a T-cell
The evaluation of PD-L1
expression in tumour cells and/
or inflammatory cells is the most
widely used predictive assay
response. A high number of mutations does not
always result in neoantigens, but it does increase
the probability of developing neoantigens. This
observation is promising as studies have shown
that mutational landscape determines sensitivity
to PD-1 blockade in NSCLC and that PD1
inhibitors in patients with a higher non-
synonymous TMB in their tumours have a greater
efficacy. We now know that it is possible to use
wide NGS panels instead of whole exome
sequencing to calculate TMB, but there are great
differences in NGS gene panel content, variant
filtering methods and definitions of high TMB
thresholds. So it is difficult to compare TMB
results across studies. In clinical practice, we need
an ‘all in one assay’ to give a complete answer to
the patient and to the oncologist. For a complete
evaluation of the genetic aberrations present in
the tumour sample (mutations, copy number
alterations, fusion genes, TMB and MSI) there are
only two validated and FDA approved NGS panels:
Foundation One Dx and MSKCC Impact. However,
the epidemiology of NSCLC makes it impossible
to use these assays in all the cases. Other panels
are currently available (ThermoFisher, for
example) or soon to be available (Illumina panel
with 500 genes). In Europe, we are not obliged to
work with companion diagnostics, but with
validated assays, therefore it is plausible that
different panels could be used. In this sense
a harmonisation process should be welcome.
Reliable assays at a sustainable cost could offer
a solution.
In immunotherapy, as in targeted therapy, the
era of ‘one size fits all’ is past and the day-to-day
work of pathologists is changing dramatically.
More and more information must be given in
the same time and NGS technology is currently
the only approach for this goal. In advanced solid
tumours diagnosed on small biopsies and/or
cytological samples, the real issue is the quantity
of the specimen.
Today more than ever is ‘the tissue the issue’.
15
HHE 2019 | hospitalhealthcare.com