Two PD-1 inhibitors – Opdivo and Keytruda – have been assessed to show considerable added benefits by Germany's G-BA.
IHS Life Sciences perspective | |
Implications | Germany's G-BA has given positive verdicts on two PD-1 inhibitors in the treatment of non-small-cell lung cancer (Opdivo) and advanced melanoma (Keytruda) for a number of patient groups. |
Outlook | The G-BA's verdicts are not only positive in the German context, in that the producers have a good position from which to start price negotiations in that country, but also because the G-BA's decisions have a strong influence on the reimbursement decisions made in other European countries. |
Germany's Federal Joint Committee (G-BA) issued on 4 February its final decision on the early benefit assessment of the Bristol-Myers Squibb (BMS, United States) PD-1 inhibitor Opdivo (nivolumab) in the treatment of locally advanced or metastatic non-small-cell lung cancer (NSCLC) with squamous-cell histology, in adult patients who had already received chemotherapy. The G-BA looked at two treatment situations: patients for whom treatment with docetaxel is indicated, in the case of which docetaxel was set as the appropriate comparator therapy, and patients for whom treatment with docetaxel is not indicted, for whom the G-BA identified best supportive care as the appropriate comparator therapy.
G-BA makes no differentiation between under-75s and over-75s
In its dossier evaluation published in November 2015, the Institute for Quality and Efficiency in Healthcare (IQWiG) divided patients for whom treatment with docetaxel was indicated between patients over 75 and those under 75 in its assessment of the extent of Opdivo's additional benefit. IQWiG decided that for patients under 75, the drug showed an indication of a major additional benefit, while in the case of patients over 75, only a hint of a non-quantifiable additional benefit was derived.
The main advantage focused on by IQWiG and the G-BA was the extension of overall survival (OS), with a median OS duration of 3.2 months for Opdivo-treated patients compared with docetaxel-treated patients. However, in contrast with IQWiG, the G-BA decided that it was inappropriate based on the submitted data to make a differential assessment of the drug's additional benefit according to patients' age; IQWiG had perceived an advantage in terms of OS for patients under 75 for Opdivo, while for those over 75, it had seen none. The G-BA decided to go against this age-based differentiation based on a number of factors, including the small number of over-75s included in the clinical study, as well as co-morbidities and the overall health status of patients.
G-BA decides Opdivo shows hint of a considerable added benefit in patients eligible for docetaxel therapy
Thus, the G-BA concluded that Opdivo demonstrated a hint of a considerable additional benefit in patients for whom docetaxel treatment was appropriate. As well as improvements in OS, the G-BA also highlighted improvements in Opdivo-treated patients in terms of side effects.
No additional benefit in patients for whom docetaxel is not indicated
Just as IQWiG did in its dossier evaluation, the G-BA decided that Opdivo showed no additional benefit in the treatment of patients for whom docetaxel is not indicated, in comparison with best-supportive care, because of a lack of appropriate data submitted. The full documentation on Opdivo's early benefit assessment in this indication can be accessed here, in German.
Another PD-1 inhibitor completes early benefit assessment
Also on 4 February, the G-BA published its final resolution on the early benefit assessment of another PD-1 inhibitor, Keytruda (pembrolizumab; Merck & Co, United States), in the treatment as monotherapy of advanced, unresectable, or metastatic melanoma in adults. Unusually, the G-BA only published a decision paper regarding this early benefit assessment, but no justification paper (Tragende Gründe).
Keytruda judged to show added benefits in two patient groups
The G-BA decided that in the case of treatment-naive patients with BRAF-V600-wild-type tumours, Keytruda showed an indication of a considerable additional benefit, compared with the appropriate comparator therapy, which in this patient group was Yervoy (ipilimumab; BMS). In the case of pre-treated patients, for whom the appropriate comparator therapy was set as patient-individual therapy, the G-BA decided that Keytruda showed a hint of a considerable additional benefit, highlighting particularly its advantages compared with Yervoy.
However, in the case of treatment-naive patients with BRAF-V600-mutated tumours, for which the appropriate comparator therapy was Zelboraf (vemurafenib; Roche, Switzerland), the G-BA decided that no additional benefit was demonstrated. In the G-BA's decision paper, it stated that for this patient group, the producer submitted no data that would justify the assessment of the drug's additional benefit in this patient group.
The G-BA gave a slightly more positive assessment of Keytruda than IQWiG in the relevant indication, since IQWiG had decided that the drug only showed a hint of a minor additional benefit in treatment-naive patients without BRAF-V600 tumour mutation (wild type). The G-BA decided that for this group, it showed an indication of a considerable additional benefit. The G-BA's decision paper on Keytruda can be accessed here, and IQWiG's dossier evaluation summary can be accessed here, in English.
Outlook and implications
In January, the G-BA decided that Opdivo showed a hint of a considerable additional benefit in some patients with advanced melanoma (see Germany: 11 January 2016: Germany's G-BA decides Opdivo shows hint of considerable additional benefit in some advanced melanoma patients). Therefore, Keytruda will face competition from Opdivo in the very same indication, with both drugs qualifying for price negotiations.
Opdivo was approved in its NSCLC indication in July 2015. The drug was not recommended in this indication by the United Kingdom's National Institute for Health and Care Excellence (NICE), although the Dutch Ministry of Health approved the drug for reimbursement in the indication. A positive verdict in Germany is a good development for the producer, considering the influence of German health technology assessment in many other European countries.
Keytruda was also approved for marketing in the European Union in July 2015. It was recommended for reimbursement by NICE, and subsequently approved for reimbursement in Norway. Similarly, a positive verdict from the G-BA has good implications with regards to the drug's future reimbursement prospects in other European countries, which defer to decisions on health technology assessment made in Germany.