key: cord-0968342-xyamsqop
authors: Choudhury, M.; Nageshwaran, S.; Muthukumar, D.
title: Evidence is Lacking for the NHS England Interim Guidance for Managing Metastatic Non-small Cell Lung Cancer in the COVID-19 Pandemic
date: 2020-07-08
journal: Clin Oncol (R Coll Radiol)
DOI: 10.1016/j.clon.2020.07.003
sha: 659a760f5a7e3038a2d2406049a9636e56fd9810
doc_id: 968342
cord_uid: xyamsqop

nan

Madam -Immunotherapy has improved non-small cell lung cancer (NSCLC) survival [1] .

[AQ1]The COVID-19 pandemic has led NHS England to suggest stopping maintenance pemetrexed and using pembrolizumab monotherapy in patients with a tumour proportion score (TPS) <50% [2] .

Before immunotherapy, pemetrexed improved median overall survival (mOS) by 2.9 months [3, 4] . In KEYNOTE-189, adding pembrolizumab improved mOS across all TPS subgroups [5] . However, the mOS in the TPS < 1% subgroup (17.2 months) was similar to pemetrexed maintenance studies. Given the higher rate of severe adverse events (71.9% versus 66.8%) and immune-related adverse events (10.9% versus 4.5%) with immunotherapy [5] , pemetrexed monotherapy may be preferable in TPS < 1% patients.

KEYNOTE-042 randomised untreated metastatic NSCLC patients to pembrolizumab monotherapy or chemotherapy, showing a mOS of 20, 17.7 and 16.7 months in TPS groups >50%, >20%, >1%, respectively [6] . This was inferior to the mOS observed in KEYNOTE-189 (TPS 1-49%: 21.8 months; TPS < 1%: 17.2 months) [5] . KEYNOTE-407 assessed triple therapy in metastatic squamous NSCLC and showed a superior progression-free survival of 7.2 months (TPS 1-49% group) and 6.3 months (TPS < 1% group) [7] compared with the progression-free survival of 6.2 months (TPS > 20% group) and 5.4 months (TPS > 1% group) in KEYNOTE-042 [6] . Critically, in KEYNOTE-042, up to 72% of the lower TPS subgroups included patients with a TPS > 50%, probably inflating the mOS observed [6] .

The survival advantages of triple therapy come at a cost of higher rates of adverse events (71.9% versus 18%), particularly myelosuppression (15% versus <2%) [5, 6] . Immunerelated adverse events can be equally challenging to manage and may present with features that overlap with COVID-19 infection. Using immunosuppression was initially thought to be detrimental with COVID-19 [8] , but the awaited RECOVERY trial publication may clarify this issue [9] .

There is limited evidence for the efficacy of pembrolizumab monotherapy in TPS 0-49%. The European Medicines Agency has declined licensing for this indication [10] . Despite interim guidance, there is an efficacy and safety trade-off that must be acknowledged.

The authors declare no conflicts of interest M. Choudhury *, S. Nageshwaran †, D. Muthukumar *

Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer

Interim treatment change options during the COVID-19 pandemic endorsed by NHS England

Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study

The PARAMOUNT trial: a phase III randomized study of maintenance pemetrexed versus placebo immediately following induction first-line treatment with pemetrexed plus cisplatin for advanced nonsquamous nonsmall cell lung cancer

KEYNOTE-189: Updated OS and progression after the next line of therapy (PFS2) with pembrolizumab (pembro) plus chemo with pemetrexed and platinum vs placebo plus chemo for metastatic nonsquamous NSCLC

Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer

COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting?

RECOVERY trial: the UK covid-19 study resetting expectations for clinical trials

EMA does not recommend extending the use of pembrolizumab

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