BRIAN SLOMOVITZ, MD


Professor, Florida International University
Gynecologic Oncology, Broward Health

Phase II study of olaparib (O) plus durvalumab (D) and bevacizumab (B) (MEDIOLA): Initial results in patients (pts) with non-germline BRCA-mutated (non-gBRCAm) platinum sensitive relapsed (PSR) ovarian cancer (OC)
DOI: https://doi.org/10.1016/j.annonc.2020.08.953

KOL Insight and Perspective

It is established that the combination of a VEGF inhibitor and olaparib increases progression free survival in ovarian cancer patients compared with olaparib alone in women with platinum sensitive recurrent ovarian cancer. Earlier reported cohorts in this study = reported the positive outcomes of therapy with olaparib, durvalumab with and without bevacizumab in women with germline mutated platinum-sensitive recurrent ovarian cancer.  Two additional cohorts were presented at the 2020 ESMO virtual meeting; the combination of olaparib and durvalumab with and without bevacizumab in women without a germline BRCA mutation.

Patients included were BRCA wildtype by germline testing. They had platinum sensitive relapsed ovarian cancer and were naïve to PARP inhibition and checkpoint inhibition. All participants received no more than 2 lines of prior therapy. The primary objective was disease control rate with a measure of success at 80% at 24 weeks.

In women who received doublet therapy with olaparib and durvalumab, the disease control rate was 28% at 24 weeks (median PFS 5.5 months) and jumped to 77% at 24 weeks (median PFS 14.7m months) when administering triplet therapy with bevacizumab. The ORR in the group of patients receiving three drugs was 87% and a median duration of response of 11.1 months. Finally, based on genomic instability data that was obtained, it did not appear that this finding was a predictor of response to therapy.

Nausea, fatigue, anemia and diarrhea were the most common adverse events. In patients who received the triplet therapy, more than 15% experienced hypertension, mouth inflammation, proteinuria, nosebleeds, and voice impairment.

Commentary

Treatment options for the management of both platinum sensitive and platinum resistant ovarian cancer remain an unmet need. Even though the treatment of choice for women with platinum sensitive disease is to rechallenge with carboplatin or cisplatin, a number of these women may not get platinum therapy (toxicity, less than 12 months progression free survival, hypersensitivity). Therapeutic options in this scenario are limited and are similar for patients with platinum resistant disease.

PARP inhibitors and VEGF inhibitors clearly have activity in patients with ovarian cancer. In addition, there is great promise in incorporating immunotherapy as a treatment option.

This study demonstrated the efficacy and tolerability of triplet therapy in women without a germline mutation. Future studies are warranted to evaluate the role of this combination in maintenance therapy for newly diagnosed patients.

Future studies need to continue to evaluate differences in effectiveness and safety of treatment options based on age. At least for PARP inhibitors, it does not seem to have a negative effect.

Reference:

Phase II study of olaparib (O) plus durvalumab (D) and bevacizumab (B) (MEDIOLA): Initial results in patients (pts) with non-germline BRCA-mutated (non-gBRCAm) platinum sensitive relapsed (PSR) ovarian cancer (OC)

  1. Drew1, R.T. Penson2, D.M. O'Malley3, J-W. Kim4, S. Zimmermann5, P. Roxburgh6, J. Sohn7, S.M. Stemmer8, S. Bastian9, M. Ferguson10, B. You11, S. Domchek12, H. Gao13, H. Angell14, K. Meyer15, L. Opincar15, L. Ottesen14, D.O. Koralek16, S. Banerjee17