Pembrolizumab has recently been approved in combination with chemotherapy for the treatment of women with persistent, recurrent, or metastatic cervical cancer whose tumours express PD-L1. Chemotherapy with or without bevacizumab is possible. The German Institute for Quality and Efficiency in Health Care (IQWiG) has now examined in an early benefit assessment whether pembrolizumab in this combination offers patients an added benefit in comparison with other treatments.
According to the findings, there is a hint of major added benefit for pembrolizumab when it is used as first-line therapy in patients who have not yet been treated with chemotherapy. The added benefit was shown in patients for whom chemotherapy with cisplatin or carboplatin – in each case plus paclitaxel with or without bevacizumab – has so far been the suitable therapy of physician's choice.
First early benefit assessment for the therapeutic indication of cervical cancer
According to the Robert Koch Institute, around 4575 women in Germany were diagnosed with cervical cancer in 2019. About 1600 women die from this disease every year.
Pembrolizumab is a monoclonal antibody, which is used to treat many cancers. Since this year, it has also been approved for the treatment of women with recurrent or metastatic cervical cancer whose tumours express PD-L1 – in combination with chemotherapy with or without bevacizumab.
The Federal Joint Committee (G-BA) now commissioned IQWiG to conduct a dossier assessment of pembrolizumab for this therapeutic indication, specifying treatment of physician's choice as the appropriate comparator therapy. The G-BA distinguished between two options of use:
- for first-line therapy and
- after first-line chemotherapy, if further drug treatment of the cancer is an option
Hint of major added benefit in first-line therapy
In its dossier on pembrolizumab for advanced cervical cancer, the drug manufacturer submitted data from the KEYNOTE‑826 study – an ongoing, randomized, double-blind study. The comparator therapies investigated in the study include the main treatments that are an option for advanced cervical cancer that has not previously been treated with systemic chemotherapy, with the exception of chemotherapy used as a radiosensitizing agent.
These treatments are
- cisplatin plus paclitaxel with or without bevacizumab and
- carboplatin plus paclitaxel with or without bevacizumab.
The data allow the derivation of a hint of major added benefit in overall survival for women for whom one of these combinations is a suitable first-line therapy.
For other outcomes, there are both positive and negative effects: While general health status improved somewhat under pembrolizumab in women under 65 years of age, it worsened slightly in older women. Severe adverse side effects such as immune-related adverse effects (including in particular skin disorders) were more frequent under pembrolizumab than in the comparator group. In addition, more women discontinued therapy due to severe adverse effects. Overall, however, this does not call into question the major added benefit of the therapy.
No data for other patient groups
No data are available for patients for whom other treatment options would be suitable as physician's choice first-line therapy. It also remains an open question whether pembrolizumab has an advantage in the further drug treatment of advanced cervical cancer after first-line chemotherapy.
G‑BA decides on the extent of added benefit
The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G‑BA. After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.
You can find an overview of the results of IQWiG's benefit assessment in an English extract. In addition, the website informedhealth.org published by IQWiG provides easily understandable information on this benefit assessment.
