First-Line Treatment Of Cancer Research Articles

Cost-effectiveness analysis of lorlatinib and crizotinib in the first-line treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer

ABSTRACT Objectives To assess the economic value of lorlatinib and crizotinib in the first-line treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer at medical insurance negotiation prices from the viewpoint of China’s health system. Methods Based on data from the phase III clinical trial, a three-state partitioned survival model was established. In combination with parameters such as treatment costs, utility values, incidence of adverse reactions, and discount rates, the total incremental cost-effectiveness ratio (ICER) was simulated. Results The results of the fundamental analysis indicated that the patients in the lorlatinib group expended 709,671 yuan more than did the patients in the crizotinib group did but gained 3.09 quality-adjusted life years (QALYs). The ICER value was 229,782.6 yuan/QALY, which was lower than three times the per capita gross domestic product (GDP) of China. Conclusions Compared with crizotinib, lorlatinib may be a cost-effective first-line treatment choice for advanced ALK-positive NSCLC in China.

Androgen Receptor Signaling Inhibitor Withdrawal Syndrome After Castration-resistant Prostate Cancer.

Androgen-deprivation therapy is an extremely effective treatment for progressive prostate cancer. Previously, the first-line treatment for progressive prostate cancer was combined androgen blockade (CAB). If the disease progressed to castration-resistant prostate cancer, the administration of androgen receptor signaling inhibitors (ARSIs) was recommended. When elevated serum prostate-specific antigen (PSA) levels are seen during CAB treatment, it is important to suspect antiandrogen withdrawal syndrome (AWS), discontinue CAB, and monitor the changes in the serum PSA levels. If a reduction in the patient's PSA levels is subsequently observed, antiandrogens should be discontinued and the patient should be followed, but if their PSA level rises they should be transitioned to ARSI treatment. Recently, there have been reports of withdrawal syndrome (WS) after ARSI treatment. With the increased use of ARSIs, such as abiraterone acetate, enzalutamide, apalutamide, and dalorutamide, it is necessary to consider ARSI WS when a patient's serum PSA level increases during ARSI treatment. Unnecessary treatment can be avoided if the confirmation of ARSI WS is prioritized. Conversely, if it is not confirmed there is a risk that second-line treatment will be delayed. This is a review of recent studies of ARSI WS. It also discusses future prospects in this field.

Critères d’évaluation de la TEP au 18F-FDG au cours de l’immunothérapie

Checkpoint inhibitor therapy is well established as a first-line treatment for cancer, but assessing treatment response using molecular imaging is still evolving. Evaluating response during checkpoint inhibitor therapy is challenging due to induced immune responses and immune-related adverse effects, which lead to atypical response patterns compared to traditional chemotherapy. Positron emission tomography (PET) and its various radiotracers provide functional information that is valuable for early evaluation of treatment response and can offer critical insights into the efficacy of immunotherapy. Furthermore, PET can help differentiate between patients with a complete response and those with residual disease, potentially guiding clinicians in deciding whether to continue or escalate treatment. This review offers an overview of the application of PET in predicting and evaluating treatment response to immunotherapy, highlighting its potential to refine therapeutic strategies and improve patient outcomes.

Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as first-line treatment for endometrial cancer (DUO-E/GOG-3041/ENGOT-EN10): Objective response rate and duration of response by mismatch repair status

Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as first-line treatment for endometrial cancer (DUO-E/GOG-3041/ENGOT-EN10): Objective response rate and duration of response by mismatch repair status

The prognostic value of circulating minimal residual disease in first-line treatment of ovarian cancer

The prognostic value of circulating minimal residual disease in first-line treatment of ovarian cancer

Anlotinib plus penpulimab plus chemo-less therapy in first-line treatment for persistent, recurrent, or metastatic cervical cancer: A single-arm, phase II study (ALTN-AK105-II-06)

Anlotinib plus penpulimab plus chemo-less therapy in first-line treatment for persistent, recurrent, or metastatic cervical cancer: A single-arm, phase II study (ALTN-AK105-II-06)

THE CLINICAL EFFECTIVENESS OF ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER: A SYSTEMATIC REVIEW

Lung cancer presents a significant epidemiological and economic burden worldwide. This deadly type of cancer ranks second in incidence and first in mortality among all cancers. The rapid increase in new and expensive treatment options places a substantial financial strain on public healthcare systems. Given the limited healthcare resources, the economic evaluation of new cancer drugs is crucial for ensuring the sustainability of healthcare systems and improving patients' access to treatments. This study aims to systematically review health state utility values (HSUVs) associated with traditional chemotherapy and targeted therapies in the first-line treatment of advanced or metastatic non-small cell lung cancer (NSCLC). A search was conducted in PubMed, EMBASE, and BioMed databases to identify publications reporting HSUVs, and 10 studies were selected from 1319 based on predefined criteria. The study found that HSUVs for targeted therapies were consistently higher across all health states compared to traditional chemotherapy. The included publications provide a comprehensive framework of HSUVs applicable to this disease and highlight the need for more empirical research to obtain a broader range of HSUVs for NSCLC.

Cost-effectiveness analysis of atezolizumab plus bevacizumab and chemotherapy for the treatment of metastatic, persistent, or recurrent cervical cancer (BEATcc)

ABSTRACT Background The addition of atezolizumab to bevacizumab plus platinum regimen has demonstrated notable improvements in treating metastatic, persistent, or recurrent cervical cancer, but its cost-effectiveness requires further investigation. From a US payer perspective, we aimed to evaluate the cost-effectiveness of atezolizumab plus bevacizumab and chemotherapy vs. standard chemotherapy as a first-line treatment for metastatic, persistent, or recurrent cervical cancer. Methods A partitioned survival model based on the data from the BEATcc trial was used to calculate the incremental cost-effectiveness ratio (ICER), using cost and health utility information obtained from literature and publicly accessible databases. One-way and probabilistic sensitivity analyses were performed to evaluate the model’s responsiveness to variations in parameters. Results The addition of atezolizumab resulted in an additional 0.839 quality-adjusted life years (QALY) at an additional cost of $458,237, leading to an ICER of $545,943/QALY. One-way sensitivity analysis indicated that the cost of atezolizumab had the greatest impact on the ICER, followed by the utility value of progression-free survival (PFS) and follow-up costs. Probabilistic sensitivity analysis showed a 0% cost-effectiveness probability at the current willingness-to-pay (WTP) threshold of $150,000 per QALY. Conclusion Adding atezolizumab to chemotherapy is cost-prohibitive in the US and may not be cost-effective for patients.

Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer have poor outcomes. Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer. Inetetamab is a novel anti-HER2 drug, and its efficacy and safety in gastric cancer have not yet been reported. AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin (SOX) regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer. METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma were randomly divided into two groups: One group received inetetamab combined with the SOX regimen, and the other group received trastuzumab combined with the SOX regimen. After 4-6 cycles, patients with stable disease received maintenance therapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were the objective response rate, disease control rate, and adverse events (AEs). RESULTS Thirty-seven patients completed the trial, with 18 patients in the inetetamab group and 19 patients in the trastuzumab group. In the inetetamab group, the median PFS was 8.5 months, whereas it was 7.3 months in the trastuzumab group (P = 0.046); this difference was significant. The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months (P = 0. 33), and the objective response rate was 50% vs 42% (P = 0.63), respectively; these differences were not significant. Common AEs included leukopenia, thrombocytopenia, nausea, and vomiting. The incidence rates of grade ≥ 3 AEs were 56% in the inetetamab group and 47% in the trastuzumab group (P = 0.63), with no significant difference. CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer, inetetamab and trastuzumab showed comparable efficacy. The inetetamab group showed superior PFS, and both groups had good safety.

Clinical risk factors of bevacizumab-related hypertension in patients with metastatic colorectal cancer: a retrospective study.

Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, is widely used as a first-line treatment for metastatic colorectal cancer (mCRC), with hypertension being a common adverse effect. However, there is limited data on the predisposing factors contributing to bevacizumab-induced blood pressure (BP) elevation. This study aims to identify clinical risk factors associated with bevacizumab-related hypertension in patients with mCRC. This retrospective study included 178 patients treated between January and June 2020. Demographic data and medical histories were extracted from hospital electronic medical records. Among the 178 patients, 54 (30.3%) developed bevacizumab-related hypertension, with a median onset time of 48days. Univariate and multivariate analyses identified pre-existing hypertension [odds ratio (OR), 3.30; 95% confidence interval (CI), 1.56-6.99] and age ≥60years (OR, 2.04; 95% CI, 1.00-4.17) as independent risk factors for bevacizumab-related hypertension. The area under the receiver operating characteristic (ROC) curve was 0.66 (95% CI, 0.57-0.75, P < 0.001). The median overall survival (OS) for the cohort was 30.53months (95% CI, 22.23-38.84). No significant differences in OS were observed between patients with and without bevacizumab-related hypertension (31.13 vs. 27.87months, P = 0.86). Pre-existing hypertension and age ≥60years are significant clinical risk factors for bevacizumab-related hypertension in mCRC patients. Bevacizumab-related hypertension did not affect overall survival. Clinicians should closely monitor BP within the first 2months of bevacizumab treatment in high-risk patients.

Efficacy and safety of immune checkpoint inhibitors for advanced or recurrent endometrial cancer: a systematic review and network meta-analysis.

Currently, several randomized controlled trials (RCTs) have been conducted to investigate the efficacy of combining immune checkpoint inhibitors (ICIs) with chemotherapy as a first-line treatment for advanced or recurrent endometrial cancer; however, the optimal treatment strategy remains undetermined. A comprehensive search of online databases was conducted to identify RCTs published until December 31, 2023. Network meta-analysis was performed to evaluate PFS, OS, TRAEs, irAEs, and the ranking of different treatment regimens. A total of 2702 patients from five RCTs (six reports) were included in the analysis. The combination therapy of ICIs significantly prolonged PFS (HR = 0.69, 95%CI 0.63-0.76, p < 0.0001) and OS (HR = 0.73, 95%CI 0.63-0.85, p < 0.0001) in the overall population. Among the different ICIs combinations evaluated, Durva-Olap-CP exhibited superior efficacy for both PFS and OS outcomes. In the pMMR population, both Durva-Olap-CP and Pembro-CP significantly reduced the risk of disease progression or death compared to Avelu-CP and Atezo-CP treatments; however, no significant differences were observed among various ICI combination therapies in patients with dMMR. In the dMMR population, Dostar-CP demonstrates a 42.2% probability of achieving first rank in terms of PFS, whereas in the pMMR population, Pembro-CP exhibits a 60% likelihood of securing the top position. Importantly, the toxicity associated with ICIs combination therapy was manageable and well-tolerated. The combination of ICIs and chemotherapy as first-line treatment for advanced or recurrent endometrial cancer has demonstrated superior survival outcomes compared to chemotherapy alone. Durva-Olap-CP exhibited the most favorable PFS and OS benefits in the overall population. In patients with dMMR, Dostar-CP showed the greatest improvement in PFS, while Pembro-CP demonstrated the most pronounced PFS benefit in patients with pMMR.

Optimal first-line treatment for EGFR-mutated NSCLC: a comparative analysis of osimertinib and second-generation EGFR-TKIs

BackgroundOsimertinib is an irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). It is the preferred first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC) compared to first-generation EGFR-TKIs. However, limited research has compared its clinical effectiveness with second-generation (2nd G) EGFR-TKIs.Materials and methodsThis study recruited patients diagnosed with stage IIIb-IV EGFR-mutated NSCLC who received first-line treatment with either 2nd G EGFR-TKIs (afatinib and dacomitinib) or osimertinib between April 2020 and April 2023.ResultsThe final analysis included 168 patients, of whom 113 received 2nd G EGFR-TKIs (afatinib or dacomitinib) and 55 received osimertinib. The median progression-free survival (PFS) did not differ significantly between 2nd G EGFR-TKIs and osimertinib (del 19: 17.6 months; L858R: 20.0 months vs. 28.3 months, p = 0.081). In patients with the EGFR exon 19 deletion, osimertinib conferred a longer median PFS (28.3 vs. 17.6 months, p = 0.118) and time to treatment failure (30.2 vs. 22.7 months, p = 0.722) than 2nd G EGFR-TKIs. However, the differences were not statistically significant. In patients with with the EGFR exon 19 deletion and central nervous system metastasis, the median PFS did not differ significantly between those treated with osimertinib (14.3 months) and those treated with 2nd G EGFR-TKIs (17.6 months; p = 0.881). Multivariate regression analysis revealed that the NSCLC stage was the only independent negative predictor of PFS. The treatment patterns in the second line also differed significantly between groups (p = 0.008).ConclusionsThis study found comparable effectiveness between osimertinib and 2nd G EGFR-TKIs as first-line treatment for advanced EGFR-mutated NSCLC, with only the NSCLC stage identified as a negative predictor of PFS. However, whether the different second-line treatments affect overall survival should be examined.

Retrospective study assessing the role of theandrogen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy.

Despite that incorporating antiangiogenic in combination with immune-checkpoint inhibitors as the standard first-line treatment for advanced clear cell renal cell cancer (ccRCC) yields promising outcomes, these regimens often lead to significant toxicity. However, a subgroup of patients has shown responsiveness to VEGFR tyrosine-kinase inhibitors (TKIs) in monotherapy, leading tothe question ofwhether employing combination therapies can significantly enhance overall survival in all patients over monotherapy. Thus, we aim to identify gene expression signatures that can predict TKI response within subpopulations that might benefit from single-agent therapies, to minimize unnecessary exposure to combination therapies and their associated toxicities, as well as to discover new potential therapeutic targets to improve ccRCC treatment. Based on prior data, the androgen receptor (AR) might meet both conditions. We evaluated the association between AR expression, assessed through NanoString® technology-derived mRNA counts, and the clinical outcomes of 98 ccRCC patients treated with first-line antiangiogenics and determined its association with other genes implicated in ccRCC tumorigenesis. Higher AR-expression correlates significantly with better prognosis and survival based on the MSKCC risk score, and longer PFS. Furthermore, we have identified a gene set signature associated with AR-overexpression and several genes involved in angiogenesis and transcriptional targets of the hypoxia-inducible factor, a cornerstone of ccRCC. AR-overexpression and its association with other genes could favor a transcriptomic signature set to aidin identifying patients suitable for TKI in monotherapy, rather than aggressive combinations, enhancing thus, precision and personalized therapeutic decisions.

Docetaxel-tethered di-Carboxylic Acid Derivatised Fullerenes: A Promising Drug Delivery Approach for Breast Cancer.

Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63nm with a conjugation efficiency of 76.7 ± 0.14%. The designed conjugate offers pH-dependent release with significantly less plasma pH, ensuring maximum release at the target site. In-vitro cell viability studies demonstrated the enhanced cytotoxic nature of the developed nanoconjugate compared to DTX. These synthesized nanoscaffolds were highly compatible with erythrocytes, indicating the safer intravenous route administration. Pharmacokinetic studies confirmed the higher bioavailability (~ 6 times) and decreased drug clearance from the system vis-à-vis plain drug. The histological studies reveal that nanoconjugate-treated tumour cells exhibit similar morphology to normal cells. Therefore, it was concluded that this developed formulation would be a valuable option for clinical use.

First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis

This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433–0.973) and 0.682 (95% CI: 0.464–0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511–1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14–3.4) and PFS 2.13 (95% CI: 1.28–3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.

Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China

Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer. In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up. 445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia. The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer. Akeso Biopharma.

Neighboring Effect-Initiated Supramolecular Nanocomplex with Sequential Infiltration as Irreversible Apoptosis Inducer for Synergetic Chemo-Immunotherapy.

Chemotherapy-based combination regimens are recommended as first-line treatment for colorectal cancer. However, multidrug resistance (MDR) and limited drug infiltration in tumor microenvironment remain critical challenges. Herein, a pH/redox dual activated supramolecular DAS@CD-OxPt (IV) nanoparticles (NPs) via host-guest molecular recognition to achieve relay drugs delivery of active oxaliplatin (OxPt (IV)) and Src inhibitor dasatinib (DAS) between tumor cells is developed. DAS@CD-OxPt (IV) NPs exhibit prolonged circulation in the blood and intra-tumoral retention. Triggered by the endo/lysosome (pH 5.0), flexible DAS@CD-OxPt (IV) NPs exhibited proton-driven in situ assembly to form nanofiber in tumor cells. Dual chemotherapeutic agents released from DAS@CD-OxPt (IV) NPs synergistically cause irreversible DNA damage by blocking p53-mediated DNA repair. Supramolecular nanofibers can further serve as the "ammunition depot" to continuously release drugs from dying cells and transport them into neighboring tumor cells, leading to domino-like cell death and enhanced immunogenicity. Furthermore, DAS@CD-OxPt (IV) NPs combined with immune checkpoint blockade (ICB) therapy strikingly suppress CT26 tumor growth and pulmonary metastasis.

Systematic review and network meta-analysis of lorlatinib with comparison to other anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) as first-line treatment for ALK-positive advanced non-smallcell lung cancer (NSCLC)

BackgroundNext-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) (alectinib, brigatinib, and lorlatinib) demonstrate superior progression-free survival (PFS) over chemotherapy or crizotinib as first-line (1L) treatment of ALK-positive advanced non-smallcell lung cancer (NSCLC). MethodsWe conducted network meta-analyses (NMAs) comparing the relative efficacy of lorlatinib with other ALK TKIs in this indication. Evidence identified from a systematic literature review and subsequent updates formed the basis of our evidence. The primary analysis investigated PFS by independent review committee (IRC) in the intent-to-treat (ITT) population. Secondary outcomes included PFS among subgroups, intracranial time to progression (IC TTP), adverse events, and discontinuation due to adverse events. For each of the outcomes, Bayesian proportional hazards NMAs estimated the relative treatment effects.Additionally, we compared the design and results of eight published NMAs conducted for 1L ALK + advanced NSCLC to date. ResultsWe formed a network of 10 trials, allowing indirect treatment comparisons. Two trials directly compared alectinib (600 mg twice daily) to crizotinib and one trial directly compared lorlatinib to crizotinib. The results of the NMA show that the hazard ratios (95 % credible interval [CrI]) for ITT PFS IRC were 0.61 (95 % CrI: 0.39, 0.97) when comparing lorlatinib with alectinib (600 mg twice daily) and 0.57 (95 % CrI: 0.35, 0.93) when comparing lorlatinib with brigatinib.In the review of published NMAs, HRs for lorlatinib versus alectinib (600 mg twice daily) and brigatinib were compared. This comparison confirmed that each published NMA yielded similar results. ConclusionsOur NMA analysis adds to existing findings and supplements data gaps from other published NMAs. Findings from eight published NMAs consistently supported lorlatinib as a clinically effective 1L treatment for ALK + advanced NSCLC patients compared to other TKIs.

Patient-reported outcomes in patients with metastatic non-squamous non-small cell lung cancer from the randomized Phase II PERLA trial comparing first-line chemotherapy plus dostarlimab or pembrolizumab

BackgroundPERLA (NCT04581824) compared efficacy and safety of dostarlimab (DCT) or pembrolizumab (PCT) plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer. Here, we report patient-reported outcomes (PROs; exploratory analysis) from PERLA. MethodsPatients were randomized 1:1 to receive DCT or PCT every 3 weeks (Q3W) for ≤ 35 cycles [C]. PROs (EORTC QLQ-C30 and QLQ-LC13, PRO-CTCAE, FACT-GP5) were collected at baseline, Q3W until C4, Q9W until C16, Q12W until end of treatment and at 30-day safety follow-up. Change from baseline and time to deterioration (TTD) in QLQ-C30 and QLQ-LC13 were analyzed using longitudinal mixed models and Kaplan–Meier estimators, respectively. ResultsThe PRO (DCT/PCT) datasets included 102/99 patients for QLQ-C30, 96/90 for QLQ-LC13, 96/88 for PRO-CTCAE, and 95/87 for FACT-GP5. Completion rates were > 80 % to C4, then decreased in both arms. For QLQ-C30 and QLQ-LC13, most patients reported stable/improved responses at C13 (∼ 9 months on treatment), with similar responses between arms except more patients reported improvements in dyspnea (QLQ-C30: 36.4 % vs 13.0 %; QLQ-LC13: 40.6 % vs 25.0 %) and chest pain (QLQ-LC13: 34.4 % vs 10.0 %) with DCT vs PCT. TTD per QLQ-C30 and QLQ-LC13 were similar between arms, although TTD in dyspnea was longer with DCT vs PCT (QLQ-LC13: 4.24 vs 1.54 months; p = 0.0168). Most patients in both arms reported that adverse events occurred occasionally/rarely/never with moderate/mild severity. Overall, patients reported little/no bother from treatment side effects. ConclusionsDCT maintained health-related quality of life similarly to PCT and was well tolerated, supporting the PERLA primary results and dostarlimab use in future regimens.

Surufatinib plus toripalimab combined with etoposide and cisplatin as first-line treatment in advanced small-cell lung cancer patients: a phase Ib/II trial

There is still room for improvement in first-line treatment of advanced small cell lung cancer (SCLC). This trial firstly investigated efficacy and safety of antiangiogenic therapy (surufatinib) (200 mg, qd, po) plus anti-PD-1 treatment (toripalimab) (240 mg, d1, ivdrip) combined with etoposide (100 mg/m², d1-d3, iv, drip) and cisplatin (25 mg/m², d1-d3, ivdrip) for advanced SCLC as first-line treatment, which has been registered on ClinicalTrials.gov under the identifier NCT04996771. The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab. The primary endpoint was progression-free survival (PFS). The secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. All of the 38 patients were enrolled for safety analysis, while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment. After a median follow-up of 21.3 months, the ORR was 97.1% (34/35), and the DCR and the tumor shrinkage rate were both 100% (35/35). The median PFS was 6.9 months (95% CI: 4.6 m–9.2 m) and the median OS was 21.1 months (95% CI: 12.1 m–30.1 m). The 12-month, 18-month, and 24-month OS rates were 66.94%, 51.39% and 38.54%. The occurrence rate of grade ≥3 treatment-emergent adverse events (TEAEs) was 63.2% (24/38), including neutrophil count decreased (31.6%, 12/38), white blood cell count decreased (23.7%, 9/38) and platelet count decreased (10.5%, 4/38). No unexpected adverse events occurred. This novel four-drug regimen (surufatinib, toripalimab, etoposide plus cisplatin) revealed impressive therapeutic efficacy and tolerable toxicities.