The Committee for Medicinal Products for Human Use (CHMP), of the European Medicines Agency (EMA), has recommended the approval of pembrolizumab (Keytruda) therapy, in combination with chemotherapy, for treating lung cancer patients whose cancer has spread.[i] Specifically, the proposed combination therapy would be administered as the first choice of treatment in adults with non-squamous non-small cell lung cancer (NSCLC), whose tumours lack particular mutations. Expression of the PD-L1 protein (which is believed to interact with Keytruda) on tumour cells is not required for approval in patients.
Keytruda is currently approved for the treatment of several types of cancer in Europe, such as:
- Melanoma that has spread or cannot be removed with surgery;
- Non-small cell lung cancer with PD-L1 expression, which has spread or is advanced;
- Classical Hodgkin lymphoma, after failure of other particular treatments; and
- Urothelial cancer that is advanced or has spread, in patients who have previously been treated with or cannot be treated with particular chemotherapy medicines.[ii]
In all approved applications of the drug, Keytruda is the only therapy which patients receive, i.e. there are no available combination therapies. The USA has adopted a similar position to Europe on Keytruda approval, with the exception that Keytruda is also approved to be used in combination with certain chemotherapy drugs to treat lung cancer.
In edition 215 of BCDN (here), we discussed the results of KEYNOTE-189, in which Keytruda, in combination with chemotherapy drugs pemetrexed and cisplatin, were used as first-line treatment in patients with metastatic non-squamous non-small cell lung cancer.[iii]
614 patients received either Keytruda plus chemotherapy drugs, or chemotherapy drugs in isolation. A concoction of treatment was successful in extending the life of lung cancer patients, because patients who received the combination treatment had longer overall survival and progression-free survival than those treated with chemotherapy alone.
Similarly, in the earlier KEYNOTE-021 trial, 123 patients were randomly sampled to receive Keytruda with chemotherapy drugs (pemetrexed and carboplatin), or chemotherapy drugs in isolation.
55% of the Keytruda and chemotherapy group achieved objective responses, compared with 29% of patients in the chemotherapy alone group.[iv]
Interim results from the Phase 3 KEYNOTE-407 trial also show that Keytruda treatment, in combination with chemotherapy drugs, resulted in significantly longer overall survival and progression-free survival than chemotherapy alone, in patients with squamous non-small cell lung cancer[v].
KEYNOTE trial findings on combination treatment led to US approval. This has, in turn, fueled the EMA’s ‘positive opinion’ on Keytruda in combination with chemotherapy drugs.
However, their recommendation will not be sanctioned yet. Instead, it will be reviewed by the European Commission for marketing authorization in the EU and a decision on approval is expected in the next few months. The CHMP has also suggested further application of Keytruda for treating patients with head and neck squamous cell carcinoma in adults whose tumours express PD-L1, and whose tumours have progressed during / after chemotherapy; final approval is expected soon.
[i] European Medicines Agency Adopts Positive Opinion for KEYTRUDA ® (pembrolizumab) Combination with Pemetrexed and Platinum Chemotherapy for the First-Line Treatment of Metastatic Nonsquamous Non-Small Cell Lung Cancer. Merck Newsroom, 30 July 2018. https://www.mrknewsroom.com/news-release/oncology/european-medicines-agency-adopts-positive-opinion-keytruda-pembrolizumab-combi (Accessed 17 August 2018)
[ii] Keytruda (pembrolizumab). European Medicines Agency, updated 26 April 2018. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003820/human_med_001886.jsp&mid=WC0b01ac058001d124 (Accessed 4 June 2018)
[iii] Merck’s KEYTRUDA(R) (pembrolizumab) Significantly Improved Overall Survival and Progression-Free Survival as First-Line Treatment in Combination with Pemetrexed and Platinum Chemotherapy for Patients with Metastatic Nonsquamous Non-Small Cell Lung Cancer (KEYNOTE-189). MERCK Newsroom, 16 January 2018. http://www.mrknewsroom.com/news-release/research-and-development-news/mercks-keytrudar-pembrolizumab-significantly-improved-ove (Accessed 18 January 2018)
[iv] Langer, C. J. et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. The Lancet Oncology 17, 1497–1508 (2016). https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30498-3/abstract (accessed 3 June 2018)
[v] Merck’s KEYTRUDA ® (pembrolizumab) Significantly Improved Overall Survival and Progression-Free Survival as First-Line Treatment for Squamous Non-Small Cell Lung Cancer (NCLC) in Pivotal Phase 3 KEYNOTE-407 Trial. Merck Newsroom, 23 May 2018 http://www.mrknewsroom.com/news-release/oncology/mercks-keytruda-pembrolizumab-significantly-improved-overall-survival-and-prog (Accessed 2 June 2018)