Scotland first in the UK to recommend a new treatment option for lung cancer, which could help lower the risk of cancer returning
October 7, 2024 – Other, Pharmaceutical – NSCLC, Scottish Medicines Consortium, approvals, lung cancer, oncology
7 October 2024 — Scotland, UK — the Scottish Medicines Consortium has recommended MSD’s KEYTRUDA® (pembrolizumab) as monotherapy for the adjuvant treatment of adults with non-small cell lung carcinoma (NSCLC) who are at high risk of recurrence following complete resection and platinum-based chemotherapy. The Scottish Medicines Consortium restricts use to adults whose tumours express programmed death-ligand 1 (PD-L1) with less than 50% (0 to 49%) tumour proportion score (TPS).
Adjuvant therapy is additional cancer treatment given after primary treatment, such as surgery, to lower the risk of cancer returning. The acceptance of pembrolizumab as adjuvant therapy for restrictive use within NHS Scotland means that more patients in Scotland with lung cancer will be able to access a treatment that reduces the risk of their cancer returning, resulting in more positive treatment outcomes compared to the current standard of care. Scottish patients will be the first in the UK to be able to access this treatment option on the NHS.
Lung cancer is the most common cancer in Scotland and is the most common cause of cancer-related death. Scotland survival rates from lung cancer are poor, with age-standardised net survival at 36.7% for men and 44.9% for women, 1 year after diagnosis. Compared to the least deprived areas in Scotland, lung cancer is three times more common in the most deprived areas. Around 80–85% of lung cancers are non-small cell carcinoma which includes adenocarcinoma, squamous cell carcinoma and large cell carcinoma.
In a randomised, phase III study, pembrolizumab (as adjuvant therapy) was associated with statistically significant improvements in disease-free survival (DFS) over placebo in patients with completely resected stage IB-IIIA non-small cell lung carcinoma (AJCC 7th ed).
Dr Clinton Ali, Consultant Medical Oncologist in Thoracic malignancies, Beatson West of Scotland Cancer Centre, said: I welcome and embrace the decision by the SMC to recommend the use of Pembrolizumab in the adjuvant setting in resected NSCLC patients with PD-L1 TPS 0-49% who are at high risk of recurrence following complete resection and platinum-based chemotherapy. “Today’s announcement highlights the importance of sound collaborative research and clinical trials in lung cancer at a global scale in early disease, as already well demonstrated in advanced disease. Our aspirations to see improvements in the survival outcomes for patients with lung cancer in Scotland has been supported by this advancement in the standard of care for our patients and their loved ones.”
Stuart Robertson, Head of Devolved Nations, MSD UK, said: “We’re pleased that the Scottish Medicines Consortium has recommended the first adjuvant immunotherapy option for adult patients with NSCLC, with PD-L1 TPS 0-49%, following complete resection and platinum-based chemotherapy. MSD are committed to bringing further treatment options to patients that can improve survival and make a real difference to outcomes for those affected.”
The recommendation was based on data from PEARLS/KEYNOTE-091 (NCT02504372). This multicentre, randomised, triple-blind phase 3 trial enrolled 1,177 patients from 196 medical centres in 29 countries. Eligible patients were aged 18 years or older, with completely resected, pathologically confirmed stage IB (tumours of ≥4 cm in diameter), II or IIIA non-small cell lung carcinoma (NSCLC) per the American Joint Committee on Cancer staging system (7th edition) of any histology or PD-L1 expression level, and an Eastern Cooperative Oncology Group performance status of 0 or 1; adjuvant chemotherapy was to be considered for stage IB disease and was strongly recommended for stage II and IIIA disease, according to national and local guidelines. Patients were randomised 1:1 to receive pembrolizumab 200mg or placebo intravenously every 3 weeks. Treatment continued until RECIST 1. 1-defined disease recurrence as determined by the investigator, unacceptable toxicity, or approximately 1 year (18 doses).
There were dual primary efficacy endpoints:
- The 1st primary efficacy endpoint was disease-free survival (DFS) in the overall population [DFS was defined as the time from randomisation to locoregional or metastatic recurrence assessed per RECIST version 1.1 by investigator review, appearance of a second NSCLC primary or other malignancy, or death from any cause, whichever occurred first].
Results: DFS in the overall population was significantly longer in the pembrolizumab group (n=590) than in the placebo group (n=587) at median follow-up of 35.6 months. Median DFS was 53.6 months (95% CI 39.2 to not reached) in the pembrolizumab group versus 42.0 months (31.3 to not reached) in the placebo group [hazard ratio (HR), 0.76 (95% CI, 0.63‒0.91); P = 0.0014].
- The 2nd primary efficacy endpoint was DFS with PD-L1 TPS of 50% or greater [DFS was defined as the time from randomisation to locoregional or metastatic recurrence assessed per RECIST version 1.1 by investigator review, appearance of a second NSCLC primary or other malignancy, or death from any cause, whichever occurred first].
Results: DFS was improved in patients whose tumours had a PD-L1 tumour proportion score (TPS) ≥50% in the pembrolizumab group (n=168) compared with the placebo group (n=165). Median DFS was not reached in either the pembrolizumab group (95% CI 44·3 to not reached) or the placebo group (95% CI 35.8 to not reach) [HR, 0.82 (95% CI, 0.57–1.18); P = 0.14]. At the final DFS analysis, DFS in PD-L1 TPS 50%+ was not statistically significant [HR, 0.83 (95% CI 0.59-1.16); p-0.13449]. Median overall survival (and 95% CI) was not reached in either group [HR 0·87 (95% CI 0·69–1·10), p=0·11792). In patients who received adjuvant chemotherapy at the final analysis for DFS performed at a median follow up time of 46.7 months (range: 0.6 to 84.2) [HR, 0.76 (95% CI 0.64-0.91)].
Adverse events (AEs) attributed to treatment occurred in 75% of participants treated with pembrolizumab (n=580) and 52% of participants treated with placebo (n=581). They led to discontinuation in 17% in the pembrolizumab group and 3% in the placebo group. Grade ≥3 treatment-related AEs occurred in 15% of participants in the pembrolizumab group and 4% of participants in the placebo group. Treatment-related AEs led to death in 4 participants (1%) and no deaths were attributed to treatment in the placebo group.
About the Scottish Medicines Consortium
The Scottish Medicines Consortium is a committee of clinicians, pharmacists, NHS board representatives, the pharmaceutical industry and the public. Members of the committee consider a broad range of evidence in order to decide which medicines should be accepted for use by NHS Scotland. Most of the clinicians have a direct role in patient care, while our three volunteer public partners ensure the views of the Scottish public are taken into account during decision making. This wide mixture of backgrounds ensures decisions are made from a broad perspective. The committee meets once a month. Visit: scottishmedicines.org.uk.
