Top Texts from Prescrire International

NEW PRODUCTS

Assessment elsewhere

conference presentation from May 2019 reported that after half of the patients had been followed up for at least 19 months, the estimated median sur- vival in the pembrolizumab group was 22 months, versus 11months in the placebo group (p<0.00001) (8). In an analysis of the Keynote-407 trial, conducted after a median follow-up of about 8 months and the death of 205 patients, the estimated median sur- vival was 16 months in the pembrolizumab group, versus 11 months in the placebo group (p=0.0008) (6). In both trials, longer survival was observed in particular in the subgroups of patients in whom fewer than half of the tumour cells expressed PD-L1 (5,6). It has not been shown whether pem- brolizumab + chemotherapy is more effective than pembrolizumab alone in patients in whom more than half of the tumour cells express PD-L1, as this has not been evaluated in a head-to-head trial. Increased incidence of certain adverse effects. The known adverse effects of pembrolizumab are main- ly of immunological origin, with possible effects on multiple organs: pneumonitis or interstitial lung disease, myocarditis, colitis, stomatitis, gastritis, pancreatitis, hepatitis, nephritis, uveitis, vasculitis, severe cutaneous adverse reactions, encephalitis and neuropathy including Guillain-Barré syndrome, endocrinopathies including thyroid disease and diabetes, myasthenia gravis, and haemolytic an- aemia. Pembrolizumab exposes to gastrointestinal disorders, fatigue, musculoskeletal pain, allergic reactions including anaphylactic reactions, fever, and alopecia (4,9). No previously unknown adverse effects of pem- brolizumab were identified in the clinical trials de- scribed above (5,6) In these trials, about 26% of patients in the pem- brolizumab groups versus about 20% in the place- bo groups had a serious adverse effect considered treatment-related by the investigators (who did not know which treatment the patient had received). And about 20% of patients versus 7% discontinued treatment due to an adverse effect (5,6). The addition of pembrolizumab appeared to in- crease the incidence of certain adverse effects. For example, patients in the pembrolizumab group of the trial in non-squamous disease were more like- ly to have diarrhoea (reported in 31% of patients versus 21% in the placebo group), rash (25% ver- sus 17%), neutropenia (48% versus 41%) and in- creased serum creatinine (37% versus 25%). In the trial in patients with squamous cell carcinoma, those in the pembrolizumab group were more likely to have alopecia (47% versus 36%) and peripheral neuropathy (31% versus 25%) (5,6,10).

The clinical evaluation data on pembrolizumab as add-on therapy to first-line platinum-based chemo- therapy in certain types of metastatic non-small cell lung cancer were analysed by the Transparency Committee of the French National Authority for Health (HAS). Its main conclusion is that the addition of pembrolizumab represents a moderate therapeut- ic advance, provided the patient’s condition is good. The committee highlighted the lack of comparative trials of pembrolizumab + chemotherapy versus pembrolizumab alone in patients in whom more than half of tumour cells express PD-L1 (7). For patients with metastatic non-small cell lung cancer, if fewer than half of their tumour cells ex- press PD-L1, and platinum-based chemotherapy is chosen as first-line treatment, add-on therapy with pembrolizumab should be offered if the patient is sufficiently well to tolerate the increased incidence of certain adverse effects and is willing to do so. If more than half of the patient’s tumour cells express PD-L1, the addition of chemotherapy to pembrolizumab has not been shown to provide any clinical benefit as of late 2019, but this combination is likely to increase the risk of adverse effects. ©Prescrire ▶ Translated from Rev Prescrire December 2019 Volume 39 N° 434 • Pages 892-894 In practice Literature search up to 9 October 2019 In response toour request for information,MSDprovided us with no documentation on its product. 1- Prescrire Editorial Staff “Metastatic lung cancer. Pembrolizumab as first-line therapy: prolonged survival in some patients” Prescrire Int 2019; 28 (210): 302. 2- PrescrireRédaction“Pémétrexed: limiter lesatteinteshématologiques avec l’acide folique” Rev Prescrire 2017; 37 (408): 745-746. 3- Prescrire Editorial Staff“Pemetrexed. Untreated non-small cell lung cancer: just another cytotoxic drug” Prescrire Int 2009; 18 (101): 114. 4- EuropeanCommission“SPC-Keytruda” 26August 2019: 105 pages. 5- EMA - CHMP“Public assessment report for Keytruda. EMEA/H/C/ 003820/II/0043” 26 July 2018: 89 pages. 6- EMA - CHMP“Public assessment report for Keytruda. EMEA/H/C/ 003820/II/0060” 31 January 2019: 103 pages. 7- HAS - Commission de laTransparence“Avis-Keytruda” 20 February 2019 and 9 October 2019: 28 pages and 29 pages. 8- Gadgeel SMet al.“Keynote-189: updatedOS and progression after the next line of therapy (PFS2) with pembrolizumab (pembro) plus chemo with pemetrexed and platinum vs placebo plus chemo for metastaticnonsquamousNSCLC” JClinOncol 2019; 37 (15suppl):9013. 9- Prescrire Rédaction “Anti-PCD-1 ou anti-PCD-L1: nivolumab, etc.” Interactions Médicamenteuses Prescrire 2019. 10- US FDA“Full prescribing information-Keytruda” September 2019: 80 pages.

Prescrire Int • February 2020

P age 4 • P rescrire I nternational S pecial E dition 2020