Commentary: Clinical efficacy of plasmid encoding p62/SQSTM1 (Elenagen) in combination with gemcitabine in patients with platinum-resistant ovarian cancer: a randomized controlled trial

Shuyan Li¹Guanze Li^2*

• ¹The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
• ²Zhejiang Chinese Medical University, Hangzhou, China

While Krasny et al. (1) offer important insights into the use of DNA vaccines for treating platinumresistant ovarian cancer, several methodological limitations must be carefully considered to inform the further development of DNA vaccine-based interventions. The results of this randomized controlled trial (RCT) are clinically encouraging; however, the study's implementation revealed conceptual and technical limitations that warrant scholarly discussion to guide the design of more robust future trials. Critical methodological challenges With a sample size of merely 40 patients and data collected exclusively from a single country, this study's results should be interpreted with caution. The limited scale and geographic restriction may constrain the generalizability of the findings, making it difficult to extrapolate the outcomes to more diverse populations with varying demographic and genetic backgrounds. Given a median follow-up of only 13.8 months, the current study may not fully capture long-term outcomes, particularly regarding the durability of treatment responses and the occurrence of serious or late-onset adverse events. Future studies with extended follow-up are likely to provide more reliable and clinically meaningful data. Novel perspectives for future research The open-label nature of this trial, though ethically necessary, may introduce both conscious and unconscious biases in outcome assessment, thereby increasing variability in the reported results. Future studies could address these limitations by employing independent blinded reviews or other methodological safeguards to ensure more objective and reliable endpoint evaluation. In order to provide a more comprehensive evaluation of therapeutic benefit, future studies could 33 consider additional clinically relevant endpoints, including overall survival (OS), in 34 addition to progression-free survival and objective response rate. This approach aligns with the 35 design of numerous RCT(2), many of which have adopted as a key endpoint to better 36 assess long-term outcomes. 37Moreover, the article suggests that ELENAGEN not only enhances antitumor immune activation but 38 also reduces chronic inflammation, thereby improving the efficacy of chemotherapy. Therefore, 39 collecting data on inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-alpha 40 (TNF-α) in future studies will be essential for elucidating inflammation-related mechanisms. 41 We recommend collecting detailed data on BRCA mutation types among patients. Analyzing 43 outcomes stratified by BRCA status could reveal differences in treatment response and inform more 44 personalized therapeutic strategies. Notably, recent RCT(3) have shown that various BRCA mutation 45 subtypes may respond differently to specific treatment modalities, emphasizing the clinical relevance 46 of mutation-specific data. This study suggests that continuous dosing may confer a potential 47 progression-free survival (PFS) benefit in patients with gBRCA wild-type or unknown status. 48Previous study(4) has demonstrated that BRCA2 mutations are significantly associated with poorer 49 OS, highlighting the need for this investigation. 50 In previous studies (5), the p26 vaccine demonstrated antitumor efficacy and an absence of toxicity in 52 animal models of Lewis lung carcinoma, B16 melanoma, S37