P1, N=9, Completed, CicloMed LLC | Trial completion date: Dec 2022 --> Apr 2023 | Trial primary completion date: Dec 2022 --> Apr 2023

P1/2, N=18, Terminated, CicloMed LLC | Phase classification: P1b/2a --> P1/2 | N=28 --> 18 | Recruiting --> Terminated; Discontinued

P2, N=12, Completed, CicloMed LLC | Active, not recruiting --> Completed

OBSERVATION: Among available treatments, it is possible to distinguish lesion-directed therapies (cryotherapy, laser therapy, conventional photodynamic theapy and surgery when a progression to iSCC is suspected) and field-directed therapies (5-fluorouracil, diclofenac,piroxicam, imiquimod and daylight photodynamic therapy)associated to daily appropriate photoprotection...We evaluated efficacy, safety and adherence to therapy of topical ointments indicated for the treatment of the different clinico-pathologic variants of AK (focusing on tirbanibulin and 5-Fluorouracil 0.5%, Salicylic Acid 10%), providing a clinical, dermoscopic and OCT longitudinal evaluation...Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis...2021;384(6):512-520. doi:10.1056/NEJMoa2024040

Clinical responses to nivolumab and pembrolizumab, in particular, are promising...In regard with safety profile, adverse events (AEs) related to anti-PD-(L)1 are lower compared with that for platinum-based and docetaxel therapy. Toripalimab is the safest among various immunotherapy drugs...Appropriate biomarker selection will improve therapy outcomes in ICI treated NSCLC patients, particularly in cases under combinatory ICI therapy. Application of bispecific antibodies and EV-based targeted therapy are effective novel strategies to improve therapeutic outcomes in cancer patients.

Only the phase III KEYNOTE-775 trial reported a statistically significant overall survival improvement for the combination of pembrolizumab plus lenvatinib compared with docetaxel or paclitaxel regardless of MMR/MSI status. Pembrolizumab plus lenvatinib is indicated for patients with unselected pretreated metastatic endometrial cancer and pembrolizumab monotherapy is a preferred option for patients with MMRd/MSI-H tumors.

Inactivating mutations in SPOP are associated with better response to ARSI treatment in mCRPC overall. Additional analysis with a larger cohort is needed to evaluate the association of SPOP status and outcomes with docetaxel. Race-associated clinical outcomes and molecular features were observed, suggesting the benefit of biomarker-directed therapy selection for individualized patient subsets in guiding treatment decisions for mCRPC patients.

After comprehensive analysis of different risk groups, the efficacy of the high-risk group on bleomycin, cisplatin, docetaxel, doxorubicin and etoposide was better than that of the low-risk group, suggesting that risk subgroups based on risk scores play a guiding role in chemotherapy and that the high-risk group may benefit more from immunotherapy. RT-qPCR results showed that LINC00924, LINC00944, and LINC00865 were highly expressed in tumour tissues, while LINC00702 and ZFAS1 were expressed at low levels in tumour tissues. In conclusion, we were the first to discover that m7G-related lncRNAs play a vital role in the tumour immune microenvironment of gastric cancer, and a risk prediction model was established to identify patients with potential benefits from immunotherapy and predict the prognosis of GC patients.

Conversely, the secretion of interferon-γ and tumor necrosis factor-α were increased. Our study provided a promising therapeutic strategy for HNSCC.

Although only a minority of MBC patients are concerned, taxane rechallenge appears to be a pragmatic option with an acceptable tolerance, and good efficacy, especially when these drugs have shown clinical activity earlier in the disease course, and/or have been stopped for reasons other than progression.

The comparators in the untreated population were pembrolizumab + pemetrexed + chemotherapy and pembrolizumab monotherapy. The comparators for the pre-treated population were docetaxel monotherapy, docetaxel + nintedanib, and platinum-based chemotherapy ± pemetrexed...The uncertainty of the clinical evidence and the estimates of cost effectiveness were too high to be considered a cost-effective use of NHS resources. Therefore, pralsetinib was not recommended for routine use.

Finally, adipocyte CM-treated PCa cells exhibited reduced responsiveness to both docetaxel and cabazitaxel, demonstrating greater chemoresistance. Overall, these data indicate that adipose tissue can effectively contribute to PCa aggressiveness by reprogramming the cancer stem cell (CSC) machinery. Adipocytes endow prostate cancer cells with stem-like properties and mesenchymal traits, increasing their tumorigenicity, invasion and chemoresistance.

Using the resazurin-based assay, the efficacy of seven chemotherapeutic agents (cisplatin, etoposide, gemcitabine, pemetrexed, vinorelbine, docetaxel and paclitaxel) was compared in the presence or absence of the individually chosen single doses of four ICIs (nivolumab, pembrolizumab, atezolizumab and durvalumab). The immunostaining of γH2AX in treated cells confirmed that the potentiation of the chemotherapeutic cytotoxicity by durvalumab was at least partially mediated via increased DNA damage; however, this effect was strongly dependent on the chemotherapy agent and cell line used. Our future studies aim to address the specific mechanisms underlying the observed ICI-induced potentiation or depotentiation.

P1/2, N=29, Not yet recruiting, The First Affiliated Hospital of Guangzhou Medical University

They were designed to carry the chemotherapeutic drug docetaxel (DTX), the autophagy inhibitor chloroquine (CQ), and Atg5 siRNA to cancer cells. The NPs exhibited remarkable considerable therapeutic effects for treating triple-negative breast cancer (TNBC) and good biosafety. Therefore, we established a novel multifunctional nanoplatform based on CMD and PS that enhances chemotherapeutic drug sensitivity through an autophagy inhibition strategy, providing new opportunities to overcome conventional drug resistance and enhance therapeutic efficiency against TNBC.

P2, N=236, Recruiting, Shengjing Hospital | Not yet recruiting --> Recruiting

After 6 cycles of Docetaxel plus Trastuzumab the patient had complete response that was complemented with posterior surgical removal of primary tumor followed by radiotherapy directed to plastron, left supraclavicular and cervical drainage. The patient is still on Trastuzumab therapy and is free of disease in the last two years. We discuss the presentation and approach of a patient with metastatic breast cancer to parotid gland in the oligometastatic scenario.

A 52-year-old female with stage Ⅳ, bilateral, HER2-positive, breast cancer as well as bilateral axillary lymph node(LN) metastasis and bilateral pulmonary metastasis was administered trastuzumab plus pertuzumab plus docetaxel as a standard chemotherapy...Trastuzumab emtansine was then administered, and the left axillary LN metastasis contracted, however, the left breast cancer expanded, resulting in marked breast engorgement...Pathological examination then confirmed that tumor cells were no longer present in the left breast and left axillary LN. In this case T-DXd was highly effective for the local treatment of intractable, HER2-positive, breast cancer.

P3, N=558, Recruiting, Henan Cancer Hospital | Trial completion date: Sep 2023 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

P2; Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2023 --> Jan 2024

Furthermore, there was a close correlation between the sensitivity of PCa patients to bicalutamide and docetaxel and the expression levels of the eight risk genes. We found that PCa cells with a high expression of AKR1C3 have high proliferation ability and high migration ability and were insensitive to enzalutamide. AKR1C3-associated genes had a significant role in the process of PCa, immune responses, and drug sensitivity and offer the potential for a novel model for prognostic prediction in PCa.

All patients received non-platinum-based chemotherapy (anthracycline/cyclophosphamide every 3 weeks × 4 + paclitaxel weekly × 12 or docetaxel every 3 weeks × 3 [AC-T]) or platinum-based chemotherapy (carboplatin AUC 5 or 6 every 3 weeks × 4/paclitaxel weekly × 12 + anthracycline/cyclophosphamide every 3 weeks × 4 [TC-AC]). Of 171 patients, 87 (50.9%) received non-platinum-based chemotherapy, and 84 (49.1%) received platinum-based chemotherapy. In addition, 39 (22.8%) patients had gBRCA-1/2 mutations. The platinum-based chemotherapy (Odds ratio [OR], 2.79; 95% CI, 1.50– 5.20, p = 0.001) and gBRCA mutation (OR, 2.50; 95% CI, 1.19–5.24, p = 0.015) was associated with pCR.

The efficacy of mobocertinib, amivantamab and poziotinib in NSCLC with EGFR exon 20 insertion mutations is promising. However, therapies were assessed in single-arm CTs with low-quality evidence. Comparative studies with more extensive patient follow-up, larger sample size and better design are needed to reliably quantify the effect of these drugs.

Androgen deprivation therapy (ADT) plus Androgen Receptor Target Agents (ARTAs) or docetaxel are the actual standard of care in prostate cancer (PC). Several therapeutic options are available for pretreated patients: cabazitaxel, olaparib, and rucaparib for BRCA mutations, Radium-223 for selected patients with symptomatic bone metastasis, sipuleucel T, and 177 LuPSMA-617...The radionuclide Lu-PSMA-617 proved successful outcomes in pretreated mCRPC patients. Additional studies will better clarify the appropriate candidates to each strategy and the correct treatments' sequence.

Moreover, the HSV-TK/GCV suicide gene therapy strategy, mediated by PAMA-co-PLAMA-based nanocarriers, resulted in high antitumor activity in 2D and 3D culture models of HCC, which was significantly enhanced by the combination with small amounts of docetaxel. Overall, our results demonstrated the potential of primary-amine polymethacrylate-containing-glycopolymers as HCC-targeted suicide gene delivery nanosystems and highlight the importance of combined strategies for HCC treatment.

This trial will provide evidence of the benefit and safety of pembrolizumab in combination with plinabulin and docetaxel in metastatic NSCLC patients who have been exposed and developed resistance to first-line PD-1/PD-L1 inhibitor either as monotherapy or in combination with chemotherapy.

Activity of the AurA-selective inhibitor, MLN8054, was also evaluated in the Eurofins Discovery BioMAP® Diversity PLUS human primary cell phenotypic profiling service to give a broader view of its biological activity. These studies demonstrate the combined value of using the OncoPanel and BioMAP platforms to determine mechanistic, functional, and broader biological activity of therapeutic candidates in relevant cellular models for a better translational understanding of potential therapeutic capabilities and accelerate decision-making.

Drug susceptibility analysis revealed differences in the responses to general drugs (docetaxel, cyclophosphamide, 5-Fluorouracil, cisplatin, paclitaxel, and vincristine) were yielded between the two risk groups. Identifying the SRG-score signature may become a promising method for predicting the prognosis of patients with PCa and tailoring appropriate treatment strategies.

Finally, patients in the high-risk group were more susceptible to docetaxel, gefitinib, methotrexate, paclitaxel, and vinblastine. The novel crlncRNA signature prognostic model shows a greatly prognostic prediction value of BCR for PCa patients, extends our thought on the association of cuproptosis and PCa, and provides novel insights into individual-based treatment strategies for PCa.

We demonstrate that an elevated CD4/CD8 Ratio is a promising IHC-based biomarker to predict favourable treatment response to FLOT neoadjuvant chemotherapy in locally advanced gastric cancer.

Nivolumab yielded survival and quality-adjusted survival benefits at incremental cost versus docetaxel in aNSCLC. As a traditional healthcare payer perspective was applied, the true economic benefit of nivolumab may be underestimated as not all treatment benefits and costs of relevance to society were considered.

Among drugs commonly used in the treatment of lung cancer, the sensitivity of cisplatin, docetaxel, gemcitabine, gefitinib, and paclitaxel was higher in low-risk patients, and patients in the low-risk group may benefit more from imatinib. These results revealed the outstanding contribution of the CuRLs signature to the evaluation of prognosis and treatment modalities for patients with LUAD. The differences in characteristics between different risk groups provide an opportunity for better patient stratification and to explore novel drugs in different risk groups.

Additionally, androgen receptor (AR)-amplified patients do not respond well to ARSIs, and PTEN mutation are associated with poorer docetaxel response. These findings support the genetic profiling of patients with mPC after diagnosis to guide treatment stratification to customize personalized treatment.

P1/2, N=74, Active, not recruiting, Laekna Limited | Recruiting --> Active, not recruiting

P3, N=151, Active, not recruiting, Jiangsu HengRui Medicine Co., Ltd. | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2022 --> Jun 2023

Animal experiments show that BUF can inhibit the growth of drug-resistant tumors in an orthotopic model of breast cancer and decrease the expression of ABCB1. BUF can reverse ABCB1-mediated docetaxel resistance in breast cancer.

Sotorasib significantly increased progression-free survival and had a more favourable safety profile, compared with docetaxel, in patients with advanced NSCLC with the KRAS mutation and who had been previously treated with other anticancer drugs.

The drug-gene interaction analysis identified 182 potential drugs to interact with 27 target genes of miR-200b/429 with paclitaxel, doxorubicin, dabrafenib, bortezomib, docetaxel, ABT-199, eribulin, vorinostat, etoposide, and mitoxantrone emerging as the top ten best candidate drugs. Taken together, miR-200b/429 and associated hub genes can be helpful for prognostic application and clinical management of cervical cancer.

Our findings provide new insights into the potential mechanism of probiotic protection of the intestine and provide a novel therapeutic strategy to augment the chemotherapeutic treatment of tumors.

P2, N=60, Recruiting, University of Chicago | Trial primary completion date: Sep 2022 --> Sep 2023

P2; Trial completion date: Dec 2024 --> Dec 2030 | Trial primary completion date: Jun 2023 --> Jun 2025

Classical chemotherapy is based on platinum-derived drugs (cisplatin, carboplatin and oxaliplatin), taxanes (docetaxel, paclitaxel) and 5-fluorouracil. This was confirmed by in vitro assays supplying the cells with products of inhibited enzymes (NA, NMN or NAD) and restoring their tumorigenic and stemness properties. In conclusion, the coinhibition of NAMPT and NAPRT improved the efficacy of antitumor treatment, indicating that the reduction in the NAD pool is important to prevent tumor growth.