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pembrolizumab ( keytruda °) with cytotoxic drugs in metastatic lung cancer A useful first-line combination when PD-L1 expression is low

 OFFERS AN ADVANTAGE  In two clinical trials, adding pembrolizumab to first-line platinum-based chemotherapy in patients with metastatic non-small cell lung cancer extended survival by a few months. The addition of pembrolizumab increases the incidence of certain adverse effects. If over half of the patient’s tumour cells express the PD-L1 protein, the addition of platinum-based chemotherapy to pembrolizumab has not been shown to provide any clinical benefit. If fewer than half of the tumour cells express PD-L1, and platinum-containing chemother- apy is chosen as first-line treatment, pem- brolizumab add-on therapy should be offered to patients who are sufficiently well to toler- ate the added harms. KEYTRUDA° - pembrolizumab concentrate for solution for intravenous infusion ■ immunostimulant; anti-PD-1 ■ New indications: first-line treatment of adults with meta- static non-small cell lung carcinoma (NSCLC): in combination with pemetrexed and platinum chemotherapy for non- squamous NSCLC with no EGFR or ALK positive mutations; in combination with carboplatin and paclitaxel for squamous NSCLC. [EU centralised procedure] The first-choice treatment for patients with meta- static non-small cell lung cancer who have not yet received treatment at this stage of the disease is often platinum-based chemotherapy in combination with another cytotoxic drug such as paclitaxel or pemetrexed . Pemetrexed appears less effective than other cytotoxic drugs against tumours classified as squamous (1-3). But when at least half of the tumour cells express the PD-L1 protein (which binds to the PD-1 receptor), monotherapy with pembrolizumab (an immuno- stimulatory anti-PD-1 monoclonal antibody) is a first-choice option for patients who have not yet received treatment at this stage of the disease. In this situation, two clinical trials versus platinum- based chemotherapy showed that pembrolizumab monotherapy extends median survival by about Compare before deciding

1 year more than chemotherapy, without increasing the incidence of serious adverse effects (1).

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Pembrolizumab (Keytruda°, Merck Sharp & Dohme) has been authorised as add-on therapy to certain platinum-based chemotherapy regimens for first- line treatment of metastatic non-small cell lung cancer, irrespective of the proportion of tumour cells expressing PD-L1 (4). What does the addition of platinum-based chemo- therapy to pembrolizumab offer patients, compared with pembrolizumab alone, when at least half of their tumour cells express PD-L1? What does the addition of pembrolizumab to platinum-based chemotherapy offer patients when fewer than half of their tumour cells express PD-L1? What are the adverse effects of the combination of pembrolizu- mab and chemotherapy? Prolonged median survival in two double-blind clinical trials. Evaluation of pembrolizumab + platinum-based chemotherapy in patients with metastatic non-small cell lung cancer is based on two double-blind randomised trials of pembrolizumab versus placebo: one trial in 616 patients with non- squamous disease, added to the combination of a platinumcompound + pemetrexed (the“Keynote-189” trial); and one trial in 559 patients with squamous cell carcinoma, added to the combination carboplatin + paclitaxel (the “Keynote-407” trial) (4-7). In both trials, all the patients were considered well or in reasonably good general condition despite their cancer. In about 30% of cases, at least half of the patient’s tumour cells expressed PD-L1 (5,6). The results available are from protocol-planned interim analyses (5,6). As about 30% of patients in the placebo groups received pembrolizumab when their cancer worsened, the effects of pembrolizu- mab may be greater than suggested by the differ- ences observed between the groups (5,6). We found no studies that compared chemotherapy + pembrolizumab versus pembrolizumab alone in patients in whom at least half of the tumour cells expressed PD-L1. Median survival extended by a few months com- pared with placebo. In an analysis of the Keynote- 189 trial, performed after a median follow-up of about 10 months, the 6-month survival rate in the pembrolizumab group was 85%, versus 72% in the placebo group (p<0.00001) (5). The abstract of a

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