1.1 Pembrolizumab, with pemetrexed and platinum chemotherapy is recommended for use within the Cancer Drugs Fund, as an option for untreated, metastatic, non-squamous non-small-cell lung cancer (NSCLC) in adults whose tumours have no epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)-positive mutations. It is only recommended if:
pembrolizumab is stopped at 2 years of uninterrupted treatment or earlier if disease progresses and
the company provides pembrolizumab according to the managed access agreement.
1.2 This recommendation is not intended to affect treatment with pembrolizumab with pemetrexed and platinum chemotherapy that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.
Why the committee made these recommendations
Standard care in people with untreated, metastatic non-squamous NSCLC whose tumours have no EGFR- or ALK‑positive mutations is usually pemetrexed with carboplatin or cisplatin. For people who cannot tolerate this, docetaxel, gemcitabine, paclitaxel or vinorelbine with carboplatin or cisplatin can be offered. People on either of these combinations may also have pemetrexed maintenance therapy. Standard care for people whose tumours express at least a 50% tumour proportion score is usually pembrolizumab monotherapy.
Clinical-effectiveness evidence comes from an ongoing trial (KEYNOTE-189). Pembrolizumab with pemetrexed and carboplatin or cisplatin (pembrolizumab combination) is likely to improve how long people live but it is difficult to establish the size of the benefit in the long term, because the trial is ongoing. Therefore, the cost-effectiveness estimates are also very uncertain.
Pembrolizumab combination meets NICE's criteria to be considered a life-extending end-of-life treatment compared with standard care and chemotherapy but does not meet the criteria when compared with pembrolizumab monotherapy. Pembrolizumab combination has the potential to be cost effective, but more evidence from the trial is needed to address the clinical uncertainties. Therefore, pembrolizumab combination is recommended for use in the Cancer Drugs Fund for adults who have untreated, metastatic, non-squamous NSCLC whose tumours have no EGFR- or ALK-positive mutations.
Pembrolizumab should be stopped at 2 years of uninterrupted treatment or earlier if disease progresses because the clinical- and cost-effectiveness evidence was limited to 2 years of treatment and the best duration of treatment is unknown.