KEY TAKEAWAYS
- ModraDoc006 is an oral form of docetaxel, co-administered with ritonavir to increase bioavailability, and has shown activity against docetaxel-resistant prostate cancer cells.
- A randomized phase 2b study compared the efficacy of ModraDoc006/r 20-20 mg with 200-100 mg ritonavir administered bi-daily to IV docetaxel 75 mg/m2 in patients with mCRPC.
- Sixty-two patients with mCRPC, performance status 0-1, and no prior chemotherapy treatment for mCRPC were included in this study.
- The main outcome measure was rPFS according to the PCWG-3 criteria.
- The secondary endpoints included ORR, PSA-PFS, time to skeletal-related events, disease control rate, response duration, and safety evaluations.
- ModraDoc006/r exhibited a promising safety profile and efficacy comparable to IV docetaxel, with superior tolerance and fewer adverse events.
The administration of docetaxel through the intravenous (IV) route and oral prednisone is a widely accepted and recommended treatment protocol for patients suffering from metastatic castration-resistant prostate cancer (mCRPC). The medication known as ModraDoc006 is an oral form of the chemotherapy drug Docetaxel. The co-administration of ritonavir (/r) is employed to augment the bioavailability of ModraDoc006. The combination of ModraDoc006 and ritonavir has demonstrated activity in various prostate cancer cell lines resistant to docetaxel and cabazitaxel. In a randomized phase 2b study conducted on patients with metastatic castration-resistant prostate cancer (mCRPC), an oral combination of ModraDoc006/r was compared to intravenous Docetaxel. The study evaluated two doses of ModraDoc006/r, namely 30-20/200-100 mg and 20-20/200-100 mg. Information regarding the results of the lower dosage administered to a larger group is being presented. Eligible patients had metastatic castration-resistant prostate cancer (mCRPC), a performance status of 0-1, and no previous chemotherapy treatment for mCRPC. A total of sixty-two patients were included in an open-label, randomized study that compared the efficacy of ModraDoc006/r 20-20 mg in combination with 200-100 mg ritonavir administered on a bi-daily weekly schedule (“20-20/200-100 mg”) to that of IV docetaxel 75 mg/m2 given in 21-day cycles. All patients were administered 5 milligrams of oral prednisone twice daily. The main outcome measure was radiographic progression-free survival (rPFS) according to the PCWG-3 criteria. The secondary endpoints comprised objective response rate (ORR), prostate-specific antigen progression-free survival (PSA-PFS), time to skeletal-related events, disease control rate, response duration, and safety evaluations.
A cohort of 31 patients received intravenous administration of docetaxel at a dosage of 75 mg/m2, while another cohort of 31 received ModraDoc006/r at 20-20/200-100 mg. Fifty-seven cases were considered to analyze relative progression-free survival (rPFS), while the objective response rate (ORR) analysis included 32 patients with detectable diseases. The median prostate-specific antigen (PSA) level observed was 46 ng/ml, ranging from 1 to 1460 ng/ml. Eight patients had received prior therapy with enzalutamide, while ten patients had received prior therapy with abiraterone. The ModraDoc006/r treatment exhibited superior tolerance with no incidence of neutropenia or anemia of any grade, in contrast to IV docetaxel which had a 26% occurrence rate (19% ≥G3) and 16% incidence of neutropenia and anemia, respectively. The incidence of neuropathy was significantly lower at 9.7% in Group 1 patients who received ModraDoc006/r compared to 9.7% in Group 1 and 19.4% in Group 2 patients who received IV docetaxel. Similarly, the incidence of alopecia was lower at 16.1% in Group 1 and 6.5% in Group 2 patients who received ModraDoc006/r compared to 22.6% in Group 1 and 19.4% in Group 2 patients who received IV docetaxel. GI toxicities were broadly comparable with diarrhea 32% (3% ≥G3) vs. 29%, nausea 29% vs. 13%, and stomatitis 3% (G3) vs. 13% (3% ≥G3), respectively. The clinical trial ModraDoc006/r exhibited a promising safety profile and efficacy comparable to intravenous docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). This outcome presents a convincing justification for implementing an extended pivotal program. The primary clinical program objective is to evaluate the efficacy of ModraDoc006/r in comparison to the most optimal available therapy for patients with refractory metastatic castration-resistant prostate cancer (mCRPC). Active development of studies on ModraDoc006/r in other malignancies is underway.
Source: https://meetings.asco.org/abstracts-presentations/208972
Clinical Trail:https://clinicaltrials.gov/ct2/show/NCT04028388
Ulka N. Vaishampayan, Marianne Keessen, Elisabeth I. Heath, Robert Dreicer, Tomas Buchler, Péter Ferenc Árkosy, Tibor Csoszi, Pawel J. Wiechno, Denis Kholtobin, Evgeny Kopyltsov, Neal D. Shore, Aleander Nosov, Sergey Orlov, Alexey Plekhanov, Maria Smagina, Sergey Varlamov, Nicholas J. VogelzangA phase 2 randomized study of oral docetaxel plus ritonavir (ModraDoc006/r) in patients with metastatic castration-resistant prostate cancer (mCRPC)/J Clin Oncol 40, 2022 (suppl 16; abstr 5016)DOI 10.1200/JCO.2022.40.16_suppl.5016
