Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer.

BACKGROUND: No treatment has surpassed platinum-based chemotherapy in improving overall survival in patients with previously untreated locally advanced or metastatic urothelial carcinoma. METHODS: We conducted a phase 3, global, open-label, randomized trial to compare the efficacy and safety of enfortumab vedotin and pembrolizumab with the efficacy and safety of platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Patients were randomly assigned in a 1:1 ratio to receive 3-week cycles of enfortumab vedotin (at a dose of 1.25 mg per kilogram of body weight intravenously on days 1 and 8) and pembrolizumab (at a dose of 200 mg intravenously on day 1) (enfortumab vedotin-pembrolizumab group) or gemcitabine and either cisplatin or carboplatin (determined on the basis of eligibility to receive cisplatin) (chemotherapy group). The primary end points were progression-free survival as assessed by blinded independent central review and overall survival. RESULTS: A total of 886 patients underwent randomization: 442 to the enfortumab vedotin-pembrolizumab group and 444 to the chemotherapy group. As of August 8, 2023, the median duration of follow-up for survival was 17.2 months. Progression-free survival was longer in the enfortumab vedotin-pembrolizumab group than in the chemotherapy group (median, 12.5 months vs. 6.3 months; hazard ratio for disease progression or death, 0.45; 95% confidence interval [CI], 0.38 to 0.54; P<0.001), as was overall survival (median, 31.5 months vs. 16.1 months; hazard ratio for death, 0.47; 95% CI, 0.38 to 0.58; P<0.001). The median number of cycles was 12 (range, 1 to 46) in the enfortumab vedotin-pembrolizumab group and 6 (range, 1 to 6) in the chemotherapy group. Treatment-related adverse events of grade 3 or higher occurred in 55.9% of the patients in the enfortumab vedotin-pembrolizumab group and in 69.5% of those in the chemotherapy group. CONCLUSIONS: Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with untreated locally advanced or metastatic urothelial carcinoma, with a safety profile consistent with that in previous reports. (Funded by Astellas Pharma US and others; EV-302 ClinicalTrials.gov number, NCT04223856.).

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions.

BACKGROUND: Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed. METHODS: In this phase 3, international, randomized trial, we assigned in a 1:1 ratio patients with advanced NSCLC with EGFR exon 20 insertions who had not received previous systemic therapy to receive intravenous amivantamab plus chemotherapy (amivantamab-chemotherapy) or chemotherapy alone. The primary outcome was progression-free survival according to blinded independent central review. Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy. RESULTS: A total of 308 patients underwent randomization (153 to receive amivantamab-chemotherapy and 155 to receive chemotherapy alone). Progression-free survival was significantly longer in the amivantamab-chemotherapy group than in the chemotherapy group (median, 11.4 months and 6.7 months, respectively; hazard ratio for disease progression or death, 0.40; 95% confidence interval [CI], 0.30 to 0.53; P<0.001). At 18 months, progression-free survival was reported in 31% of the patients in the amivantamab-chemotherapy group and in 3% in the chemotherapy group; a complete or partial response at data cutoff was reported in 73% and 47%, respectively (rate ratio, 1.50; 95% CI, 1.32 to 1.68; P<0.001). In the interim overall survival analysis (33% maturity), the hazard ratio for death for amivantamab-chemotherapy as compared with chemotherapy was 0.67 (95% CI, 0.42 to 1.09; P = 0.11). The predominant adverse events associated with amivantamab-chemotherapy were reversible hematologic and EGFR-related toxic effects; 7% of patients discontinued amivantamab owing to adverse reactions. CONCLUSIONS: The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.).

Peripheral Blasts in a Patient Receiving Chemotherapy.

An older patient with stage II bladder carcinoma presented with 1 week of fatigue and 2 days of dyspnea on exertion. He was receiving carboplatin/gemcitabine with 6 mg of pegylated G-CSF chemotherapy; his white blood cell count was elevated, hemoglobin low, and ferritin notably increased. What is the diagnosis and what would you do next?

Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer.

Netrin-1 is upregulated in cancers as a protumoural mechanism1. Here we describe netrin-1 upregulation in a majority of human endometrial carcinomas (ECs) and demonstrate that netrin-1 blockade, using an anti-netrin-1 antibody (NP137), is effective in reduction of tumour progression in an EC mouse model. We next examined the efficacy of NP137, as a first-in-class single agent, in a Phase I trial comprising 14 patients with advanced EC. As best response we observed 8 stable disease (8 out of 14, 57.1%) and 1 objective response as RECIST v.1.1 (partial response, 1 out of 14 (7.1%), 51.16% reduction in target lesions at 6 weeks and up to 54.65% reduction during the following 6 months). To evaluate the NP137 mechanism of action, mouse tumour gene profiling was performed, and we observed, in addition to cell death induction, that NP137 inhibited epithelial-to-mesenchymal transition (EMT). By performing bulk RNA sequencing (RNA-seq), spatial transcriptomics and single-cell RNA-seq on paired pre- and on-treatment biopsies from patients with EC from the NP137 trial, we noted a net reduction in tumour EMT. This was associated with changes in immune infiltrate and increased interactions between cancer cells and the tumour microenvironment. Given the importance of EMT in resistance to current standards of care2, we show in the EC mouse model that a combination of NP137 with carboplatin-paclitaxel outperformed carboplatin-paclitaxel alone. Our results identify netrin-1 blockade as a clinical strategy triggering both tumour debulking and EMT inhibition, thus potentially alleviating resistance to standard treatments.

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.

BACKGROUND: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear. METHODS: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort. RESULTS: In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy. CONCLUSIONS: In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer.

BACKGROUND: Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer. METHODS: We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. The primary end points were progression-free survival as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and overall survival. Safety was also assessed. RESULTS: Of the 494 patients who underwent randomization, 118 (23.9%) had mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors. In the dMMR-MSI-H population, estimated progression-free survival at 24 months was 61.4% (95% confidence interval [CI], 46.3 to 73.4) in the dostarlimab group and 15.7% (95% CI, 7.2 to 27.0) in the placebo group (hazard ratio for progression or death, 0.28; 95% CI, 0.16 to 0.50; P<0.001). In the overall population, progression-free survival at 24 months was 36.1% (95% CI, 29.3 to 42.9) in the dostarlimab group and 18.1% (95% CI, 13.0 to 23.9) in the placebo group (hazard ratio, 0.64; 95% CI, 0.51 to 0.80; P<0.001). Overall survival at 24 months was 71.3% (95% CI, 64.5 to 77.1) with dostarlimab and 56.0% (95% CI, 48.9 to 62.5) with placebo (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.87). The most common adverse events that occurred or worsened during treatment were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group than in the placebo group. CONCLUSIONS: Dostarlimab plus carboplatin-paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR-MSI-H population. (Funded by GSK; RUBY ClinicalTrials.gov number, NCT03981796.).

Genetic variations in ABC transporter genes as a predictive biomarker for toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

ATP-binding cassette (ABC) transporters are expressed in various human tissues and play a vital role in the efflux of various chemotherapeutic drugs. The current study has assessed genetic variants of ABCB1, ABCC1, ABCC2, and ABCG2 genes in 407 lung cancer patients undergoing platinum-based doublet chemotherapy. The association of ABCB1 (C1236 T, C3435 T, and G2677 T/A), ABCC1 (G3173 A and G2168 A),ABCC2 (G4544 A), and ABCG2 (C421 A) polymorphisms with chemotherapy-induced adverse events were assessed, and statistical analysis was conducted. Our data showed that patients harboring heterozygous (GA) genotype for ABCC1 G3173 A had an increased risk of developing leukopenia (odds ratio [OR] = 1.88, p = 0.04) and anemia (adjusted odds ratio [AOR] = 2.70, p = 0.03). For ABCC2 G4544 A polymorphism, patients harboring one copy of the mutant (GA) allele showed an increased risk of developing anemia (OR = 4.24, p = 0.03). After adjusting with various confounding factors, the heterozygous (GA) genotype showed a 5.63-fold increased risk of developing anemia (AOR = 5.63, p = 0.03). The ABCB1 G2677 A (OR = 0.37, p = 0.008) and ABCC1 G3173 A (OR = 0.54, p = 0.04) polymorphism showed a lower incidence of developing nephrotoxicity. In ABCG2 C421 A polymorphism, patients harboring heterozygous (CA) genotype had a lower incidence of having diarrhea (OR = 0.25, p = 0.04). An increased risk of having diarrhea was observed in the heterozygous genotype (GA) for ABCC1 G3173 A polymorphism (AOR = 2.78, p = 0.04). An increased risk of liver injury was found in the patients carrying heterozygous genotype of the ABCC1 G3173 A (OR = 2.06, p = 0.02) and ABCB1 C1236 T (OR = 1.85, p = 0.01). This study demonstrates the role of polymorphic variations in ABCB1, ABCC1, ABCC2, and ABCG2 in predicting hematological, nephrotoxicity, gastrointestinal, and hepatotoxicity.

Time to Optimize Deescalation Strategies in Triple-Negative Breast Cancer?

Pathologic response serves as a tool to optimize escalation and deescalation of adjuvant treatment. Neoadjuvant carboplatin-taxane combination is a promising chemotherapy deescalation strategy for triple-negative breast cancer. Many key points, such as trial design/patient selection, response biomarkers, role of immunotherapy, and patient advocate input, will have to be carefully considered in order to advance neoadjuvant chemotherapy deescalation investigations. See related article by Gluz et al., p. 4995.

Variants of ERCC5 and the outcome of platinum-based regimens in non-small cell lung cancer: a prospective cohort study.

Excision repair complementary complex 5 (ERCC5) is an important component in the repair pathway of platinum-induced damage. The current study evaluated the effect of ERCC5 variants (rs751402 and rs1047768) on the clinical outcome of platinum-based regimens in non-small cell lung cancer (NSCLC) patients. A prospective, cohort study was conducted on 57 newly diagnosed NSCLC Egyptian patients. Patients received either cisplatin or carboplatin-based chemotherapy. DNA was extracted and the variants were analyzed using real time PCR. This study found no significant difference between the studied variants and patients' response to chemotherapy, progression-free survival (PFS) or overall survival (OS). However, a statistically significant association was found between the histologic subtypes and the studied variants (p = 0.028 and 0.018 for rs751402 and rs1047768, respectively). A statistically significant association was evident between the type of the allele present in the studied polymorphisms, p value = 0.000040. Moreover, the minor allele frequency (MAF) of the studied variants rs751402 and rs1047768 were similar to those of African and European populations, respectively. Results of this study have concluded that ERCC5 variants did not affect the clinical outcome of platinum-based chemotherapy in NSCLC. A significant coinheritance was found between the two variants of ERCC5. Moreover, the similarity between the MAF of the studied variants and the African or European population can guide future research when extrapolating data from African European populations to their Egyptian counterparts.

De-escalated Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer (TNBC): Impact of Molecular Markers and Final Survival Analysis of the WSG-ADAPT-TN Trial.

PURPOSE: Although optimal treatment in early triple-negative breast cancer (TNBC) remains unclear, de-escalated chemotherapy appears to be an option in selected patients within this aggressive subtype. Previous studies have identified several pro-immune factors as prognostic markers in TNBC, but their predictive impact regarding different chemotherapy strategies is still controversial. EXPERIMENTAL DESIGN: ADAPT-TN is a randomized neoadjuvant multicenter phase II trial in early patients with TNBC (n = 336) who were randomized to 12 weeks of nab-paclitaxel 125 mg/m2 + gemcitabine or carboplatin d 1,8 q3w. Omission of further (neo-) adjuvant chemotherapy was allowed only in patients with pathological complete response [pCR, primary endpoint (ypT0/is, ypN0)]. Secondary invasive/distant disease-free and overall survival (i/dDFS, OS) and translational research objectives included quantification of a predictive impact of markers regarding selection for chemotherapy de-escalation, measured by gene expression of 119 genes (including PAM50 subtype) by nCounter platform and stromal tumor-infiltrating lymphocytes (sTIL). RESULTS: After 60 months of median follow-up, 12-week-pCR was favorably associated (HR, 0.24; P = 0.001) with 5y-iDFS of 90.6% versus 62.8%. No survival advantage of carboplatin use was observed, despite a higher pCR rate [HR, 1.04; 95% confidence interval (CI), 0.68-1.59]. Additional anthracycline-containing chemotherapy was not associated with a significant iDFS advantage in pCR patients (HR, 1.29; 95% CI, 0.41-4.02). Beyond pCR rate, nodal status and high sTILs were independently associated with better iDFS, dDFS, and OS by multivariable analysis. CONCLUSIONS: Short de-escalated neoadjuvant taxane/platinum-based combination therapy appears to be a promising strategy in early TNBC for using pCR rate as an early decision point for further therapy (de-) escalation together with node-negative status and high sTILs. See related commentary by Sharma, p. 4840.

Dose Modification of Etoposide plus Platinum in Elderly Patients with Extensive-Disease Small-Cell Lung Cancer.

BACKGROUND: Elderly patients with extensive-disease small-cell lung cancer (ED-SCLC) have a high risk of chemotherapy toxicity due to multiple comorbidities and poor performance status. Although dose modification is often used to avoid toxicity in elderly patients with ED-SCLC, there is little data on the effect of initial dose-reduced chemotherapy on survival outcomes. METHODS AND PATIENTS: We retrospectively reviewed 100 elderly patients (≥70 years) with ED-SCLC who received first-line etoposide plus platinum chemotherapy between January 2006 and December 2020. RESULTS: The median age was 74 years. Eighty-nine patients (89%) had a history of smoking, and 38 (38%) had chronic lung disease. Thirty-four patients (34%) received dose-reduced etoposide plus platinum in the first cycle. The dose-reduced group had significantly higher age, lower body mass index, and poor Eastern Cooperative Oncology Group Performance Score. There were no significant differences in survival outcomes between the dose-reduced and full-dose chemotherapy (median overall survival [OS], 4.9 vs. 6.5 months, p = 0.440; median progression-free survival [PFS], 3.7 vs. 4.6 months, p = 0.272). In multivariate analyses, DR in the first cycle (hazard ratio 0.519, 95% CI: 0.269-1.000, p = 0.050) was significantly associated with OS. Following a subgroup analysis of 59 patients who received minimum four cycles, no significant differences in survival outcomes between the two groups (median OS, 10.9 vs. 9.4 months, p = 0.817; median PFS, 6.3 vs. 6.5 months, p = 0.902) were noted. CONCLUSIONS: The dose-reduced chemotherapy with first-line etoposide plus platinum had non-inferior survival outcomes compared to the full-dose chemotherapy in elderly patients with ED-SCLC.

Ovarian toxicity of carboplatin and paclitaxel in mouse carriers of mutation in BRIP1 tumor suppressor gene.

More than 10% of women diagnosed with breast cancer during reproductive age carry hereditary germline pathogenic variants in high-penetrance BRCA genes or in others genes involved in DNA repair mechanisms such as PALB2, BRIP or ATM. Anticancer treatments may have an additional negative impact on the ovarian reserve and subsequently on the fertility of young patients carrying such mutations. Recently, the combination of carboplatin and paclitaxel is being recommended to these BRCA-mutated patients as neoadjuvant therapy. However, the impact on the ovary is unknown. Here, we investigated their effect of on the ovarian reserve using mice carriers of BRCA1-interacting protein C-terminal helicase-1 (BRIP1) mutation that plays an important role in BRCA1-dependent DNA repair. Results revealed that the administration of carboplatin or paclitaxel did not affect the ovarian reserve although increased DNA double-strand breaks were observed with carboplatin alone. Co-administration of carboplatin and paclitaxel resulted in a significant reduction of the ovarian reserve leading to a lower IVF performance, and an activation of the PI3K-Pten pathway, irrespective of the genetic background. This study suggests that co-administration of carboplatin and paclitaxel induces cumulative ovarian damage and infertility but a heterozygote genetic predisposition for DNA damage related to BRCA1 gene function does not increase this risk.

A prospective phase II clinical trial identifying the optimal regimen for carboplatin plus standard backbone of anthracycline and taxane-based chemotherapy in triple negative breast cancer.

Addition of platinums to combination chemotherapy for triple negative breast cancer (TNBC) has shown efficacy and is increasingly accepted in the clinic, yet optimal delivery is unknown. A prospective clinical trial with TNBC patients was conducted to determine the optimal chemotherapy regimen to deliver carboplatin with standard dose dense ACT. Tissue microarray was conducted to isolate markers indicative of response to treatment. 90 TNBC patients were enrolled onto our trial. The most successful version placed the carboplatin on the second and final paclitaxel treatment with liberal hematological parameters. Our final regimen had the lowest grade 3 or 4 toxicities, no delays, no dose reductions of carboplatin, and 32% reduction in paclitaxel doses. Stage I (AJCC7) patients did well with carboplatin-based chemotherapy with zero relapse rate. Reduction in protein levels of androgen receptor and PD-L1 were found to be potential indicators of patient relapse. We have optimized a protocol for the addition of carboplatin to standard of care chemotherapy in TNBC patients. Early data indicates reduced protein levels of androgen receptor and PD-L1 as indicators of response to treatment.Trial registration This trial was registered at Canadian Cancer Trials. http://www.canadiancancertrials.ca/.

Sister Mary Joseph nodule as cutaneous manifestations of metastatic ovarian cancer: A case report and review of the literature.

RATIONALE: The Sister Mary Joseph's nodule is an umbilical nodule resulting from the metastasis of malignant tumors in the pelvic and/or abdominal cavity. Sister Mary Joseph's nodules are very rare, and the morphology of the skin lesions is not specific and is easily misdiagnosed. Here, we report a case of cutaneous manifestations of metastatic ovarian cancer. PATIENT CONCERNS: The patient was admitted to our hospital because of abdominal distention, and a nodule was found in the umbilicus. A computerized tomography scan of the entire abdomen showed nodular soft tissue in the subcutaneous fat space of the umbilical area and multiple pelvic masses, which were suspected metastases of peritoneal and omentum ovarian cancer. INTERVENTIONS: To confirm the pathological diagnosis, posterior fornix puncture was performed. Pathological biopsy showed adenocarcinoma. Histological examination revealed a mass arising from high-grade serous carcinoma of the ovary. The patient received 2 cycles of chemotherapy with paclitaxel liposomes and carboplatin and underwent interval debulking surgery. Postoperative pathology was consistent with high-grade serous carcinoma of the ovary. Cancer involvement was observed in umbilical lesions. After the operation, the patient was given 6 cycles of chemotherapy with paclitaxel liposomes and carboplatin. OUTCOMES: The patient underwent follow-up until October 2020. A computerized tomography scan of the entire abdomen showed that the lymph nodes in the abdominal cavity were larger than before, suggesting a platinum-sensitive relapse. After receiving the same regimen of chemotherapy, carbohydrate antigen 125 dropped to the normal range, and consolidated treatment was administered for 3 cycles. Owing to her BRCA1 mutations, olaparib was administered for maintenance treatment. Until now, she had been in the outpatient clinic for regular follow-up visits. LESSONS: The umbilicus remains an infrequently examined area, which cannot be underestimated and warrants careful clinical follow-up and histological evaluation, as appropriate.

TUSC2 immunogene enhances efficacy of chemo-immuno combination on KRAS/LKB1 mutant NSCLC in humanized mouse model.

KRAS/LKB1 (STK11) NSCLC metastatic tumors are intrinsically resistant to anti-PD-1 or PD-L1 immunotherapy. In this study, we use a humanized mouse model to show that while carboplatin plus pembrolizumab reduce tumor growth moderately and transiently, the addition of the tumor suppressor gene TUSC2, delivered systemically in nanovesicles, to this combination, eradicates tumors in the majority of animals. Immunoprofiling of the tumor microenvironment shows the addition of TUSC2 mediates: (a) significant infiltration of reconstituted human functional cytotoxic T cells, natural killer cells, and dendritic cells; (b) induction of antigen-specific T cell responses; (c) enrichment of functional central and memory effector T cells; and (d) decreased levels of PD-1+ T cells, myeloid-derived suppressor cells, Tregs, and M2 tumor associated macrophages. Depletion studies show the presence of functional central and memory effector T cells are required for the efficacy. TUSC2 sensitizes KRAS/LKB1 tumors to carboplatin plus pembrolizumab through modulation of the immune contexture towards a pro-immune tumor microenvironment.

Bevacizumab in combination with paclitaxel and platinum for previously treated advanced thymic epithelial tumors.

There are no optimal regimens for advanced thymic epithelial tumors (TETs) when frontline chemotherapy fails. In this study, we aimed to assess the activity of Bevacizumab in combination with a routine chemotherapeutic regimen. Patients with advanced TETs who had failed after previous chemotherapy were enrolled in this study. Paclitaxel (160 mg/m2) and cisplatin (70 mg/m2) or carboplatin (area under the curve, 6) plus Bevacizumab (7.5 mg/kg) were intravenously injected on day 1.The treatment was repeated every 3 weeks until the disease progressed or intolerable toxicities occurred. Between March 2018 and August 2020, a total of 49 patients (21 thymoma and 28 thymic carcinoma) received the new treatment. There were 28 men and 21 women with a median age of 50 years (range: 21-73 years). The median number of cycles was 3 (range: 1-6) per patient. The objective response rate (ORR) for all patients was 43% (21/49). The ORRs for thymoma and thymic carcinoma were 24% and 57%, respectively. The median progression-free survival for thymoma and thymic carcinoma was 6 and 8 months, respectively. Hematological toxicities were the main side effects. Paclitaxel and platinum plus Bevacizumab showed promising effects in refractory or relapsed advanced TETs without severe toxicity. Even when applied as salvage therapy, this regimen resulted in a better ORR than frontline chemotherapy.

Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment.

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC. METHODS: Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, [Formula: see text] 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response. DISCUSSION: A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov on October 1st, 2020 with Identifier: NCT04572100 .

A 33-Year-Old Man With Chest Pain.

CASE PRESENTATION: A 33-year-old man was admitted with a 4-week history of intermittent, right-sided chest pain. Two weeks before the incident, he had completed a 10-day course of levofloxacin for a presumed right-sided pneumonia without much improvement. He denied any dyspnea, cough, sputum production, hemoptysis, night sweats, or weight loss. He was an active smoker with a 20-pack-year smoking history and 1-year history of vaping nicotine.

Differences in the Therapeutic Effect of Chemotherapy Regimens for Concurrent Chemoradiotherapy of Locally Advanced Non-small Cell Lung Cancer.

BACKGROUND/AIM: The optimal chemotherapy for concurrent chemoradiotherapy (cCRT) of lung cancer is still unclear. PATIENTS AND METHODS: We investigated the therapeutic effect of different chemotherapy regimens for cCRT of lung cancer in 65 patients at our hospital. RESULTS: Of the 65 patients, 53 were male and 12 female. The median age was 64 years and 58 participants had a smoking history. The histological type was adenocarcinoma in 34 cases, squamous cell carcinoma in 22 cases, and others in 9 cases. Induction therapy consisted of cisplatin plus vinorelbine (CDDP+VNR) in 50 cases, and weekly carboplatin plus paclitaxel (CBDCA+PTX) in 15 cases. In all patients, the overall response rate, disease control rate, median progression survival, and median overall survival were 78.5%, 95.4%, 337 days, and 1,037 days, respectively. The median progression-free survival was 337 days in total; it was significantly longer for CDDP+VNR than CBDCA+PTX. The median overall survival was 1,037 days in total; it tended to be slightly longer for CDDP+VNR than CBDCA+PTX. CONCLUSION: Different chemotherapy regimens for cCRT possibly have different therapeutic effects.