“Early Benefit Assessment of Olaparib for Metastatic Castration-Resistant Prostate Cancer: Age and Pretreatment as Crucial Factors in Additional Benefit Compared to Appropriate Comparator Therapy, According to Institute for Quality and Efficiency in Health Care (IQWiG)”

2023-04-17 15:17:00

Olaparib is approved for several indications. In an early benefit assessment, the Institute for Quality and Efficiency in Health Care (IQWiG) examined whether the drug in combination with abiraterone and prednisone or prednisolone in adults with metastatic castration-resistant prostate cancer (mCRPC) for whom chemotherapy is not indicated has an additional benefit compared to appropriate comparator therapy.

Accordingly, there is a hint of a minor added benefit for those under 65 years of age who have not previously been treated, but there is a hint of a lesser benefit in comparison with the appropriate comparator therapy for older people who have not previously been treated. For pretreated patients, an added benefit is not proven due to a lack of relevant data.

Pre-treatment and age are crucial

The Federal Joint Committee (G‑BA) distinguished between two groups of patients. For adults with previously untreated mCRPC, the appropriate comparator therapy is therapy according to medical prescriptions. In adults with previously treated mCRPC, treatment with olaparib should be compared with patient-specific therapy, taking into account previous therapy and BRCA1/2 mutation status.

For treatment-naïve patients, the manufacturer uses data from PROpel, a double-blind, randomized controlled trial that compared olaparib with abiraterone and prednisone or prednisolone in addition to abiraterone and prednisone or prednisolone. The patients showed disease progression at the start of the study – despite medical or surgical castration, which had to be continued during the study. Whether this was realized in all patients and whether only men were included for whom chemotherapy – as required for the use of olaparib – was not an option, cannot be inferred from the study documentation with certainty. This reduces the certainty of conclusions, so that a maximum of clues can be derived from the study.

Age is important for the endpoints overall survival and symptomatic skeletal-related events: For those under 65 years of age, there is a hint of an added benefit of olaparib in overall survival. There is no survival advantage for older patients, but there is a hint of a minor added benefit in symptomatic skeletal events.

In terms of health-related quality of life and side effects, some results differ according to the organs in which there were metastases at the start of the study (only in the bones or also in the abdomen and other locations). There are both advantages and disadvantages of the new medication. Irrespective of age and type of metastases, however, more serious adverse events, treatment discontinuations due to adverse events and, in particular, severe pulmonary embolism and blood count changes occurred with olaparib.

Overall, there is a hint of a minor added benefit for patients under 65 years of age, while for older patients there is a hint of a lesser benefit of treatment with olaparib compared with the appropriate comparator therapy.

Advantages or disadvantages for pretreated unknown

The patients included in the PROpel study had not yet received any pretreatment for the metastatic disease stage, so this study does not allow any conclusions to be drawn about pretreated patients. The manufacturer did not provide any other adequate data for these patients in its dossier. It remains unclear why he did not name a potentially relevant study sponsored by him (Study 8), which was also used in the approval of olaparib, in the study list and did not submit any documents on it.

Based on the information available, it was not possible to assess whether the appropriate comparator therapy for previously treated patients was implemented in this study—at least for a subpopulation. The result is therefore: For adults with previously treated mCRPC, an added benefit of olaparib plus abiraterone plus prednisone or prednisolone in comparison with the appropriate comparator therapy is not proven.

G‑BA decides on the extent of the additional benefit

The dossier assessment is part of the early benefit assessment in accordance with the Drug Market Reorganization Act (AMNOG), for which the G‑BA is responsible. After publication of the dossier assessment, the G‑BA carries out a commenting procedure and makes a final decision on the extent of the additional benefit.

The following summary provides an overview of the results of the IQWiG benefit assessment. On the website gesundheitsinformation.de published by IQWiG you will also find generally understandable information.