SAKK57/16 Nab-paclitaxel and Gemcitabine in Soft Tissue Sarcoma (NAPAGE): a phase I/II trial (1).
This study investigated the combination of nab-paclitaxel (nab-pc) and gemcitabine as a treatment for patients with pretreated soft tissue sarcoma (STS). The study was structured as a phase Ib/II clinical trial, encompassing both a dose-de-escalation phase and an expansion phase. In phase I, nab-pc was administered at 150 mg/m² combined with gemcitabine at 1000 mg/m² every two weeks, continuing until disease progression or unacceptable toxicity was observed. This dosage was recommended for phase II after no dose-limiting toxicity (DLT) or discontinuations due to adverse events (AEs) were recorded.
The results of the study are as follows: The 3-month progression-free rate (PFR) was 56.4% (95% CI: 39.6-72.2%). The 3-month and 6-month progression-free survival (PFS) rates were 58.4% (95% CI: 41.3-72.1%) and 44.6% (95% CI: 28.4-59.5%), respectively. The median PFS was 5.3 months (95% CI: 1.4-8.2), and the median overall survival (OS) was 12.8 months (95% CI: 10.5-39.2). Regarding safety, the most common treatment-related grade ≥ 3 adverse event was neutropenia (18%), followed by anemia (2.6%), hypertension (2.6%), and increased alanine aminotransferase (2.6%). Grade 1 and 2 peripheral sensory neuropathy (PNP) occurred in 15.4% and 20.5% of patients, respectively, with no reported grade 3-4 PNP.
The study concluded that the combination of nab-paclitaxel and gemcitabine is safe and shows promising activity in pretreated STS patients, with manageable toxicity. The findings suggest that this regimen is a viable candidate for further exploration in the treatment of soft tissue sarcoma.
Clinical Significance
The standard treatment for STS typically involves a combination of surgery, radiation therapy, and chemotherapy, depending on the stage and type of sarcoma. Chemotherapy for advanced STS often includes agents such as doxorubicin and ifosfamide. However, it's important to note that the treatment landscape for STS is quite diverse due to the heterogeneity of this group of cancers, and the choice of treatment is heavily influenced by the specific subtype of sarcoma, the patient's overall health, and the cancer's location and stage.
Regarding the impact of the results from the study "SAKK57/16 Nab-paclitaxel and Gemcitabine in Soft Tissue Sarcoma (NAPAGE): a phase I/II trial," several points are noteworthy:
Efficacy in Pretreated Patients: The study focuses on patients with pretreated STS, a group that often has limited treatment options. The observed efficacy, including the progression-free rate and survival outcomes, in this population suggests a potentially valuable treatment avenue for patients who have exhausted other options.
Safety and Tolerability: The combination of nab-paclitaxel and gemcitabine demonstrated manageable toxicity. This aspect is crucial in oncology, where balancing treatment efficacy with quality of life is a significant concern.
Progression-Free and Overall Survival Rates: The reported progression-free survival (PFS) and overall survival (OS) rates are encouraging, particularly in the context of a pretreated patient population. These rates are critical indicators of the treatment's potential effectiveness.
Need for Further Research: While the results are promising, it's important to remember that this is a phase I/II trial. Further research, particularly phase III trials involving larger patient populations and possibly comparing the new regimen directly against the current standard treatments, is needed to definitively establish the efficacy and safety of this combination therapy in a broader context.
Potential Impact on Treatment Guidelines: If subsequent studies support these findings, this combination therapy could become a new standard of care for pretreated STS patients or be included as an additional option in treatment guidelines.
In summary, the results of this study are indeed impactful in the realm of STS treatment, especially for patients who have previously undergone treatment. The clinical significance of these findings lies in the potential for a new, effective treatment option for patients with this type of cancer, particularly those who have been pretreated, offering a balance between efficacy and manageable side effects. However, the full impact on the standard of care will depend on the outcomes of larger, more definitive trials.
Digklia A, Kollár A, Dietrich D, Kronig MN, Britschgi C, Rordorf T, et al. SAKK57/16 Nab-paclitaxel and Gemcitabine in Soft Tissue Sarcoma (NAPAGE): a phase I/II trial. Eur J Cancer. 2024;197:113470.