Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study. Huh Warner K,Brady William E,Fracasso Paula M,Dizon Don S,Powell Matthew A,Monk Bradley J,Leath Charles A,Landrum Lisa M,Tanner Edward J,Crane Erin K,Ueda Stefanie,McHale Michael T,Aghajanian Carol Gynecologic oncology OBJECTIVE:Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). METHODS:Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 10 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). RESULTS:Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3-12.1) and median PFS was 2.8 months (95% CI: 2.6-3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. CONCLUSION:At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma. 10.1016/j.ygyno.2020.06.493

Concordance Study Between IBM Watson for Oncology and Clinical Practice for Patients with Cancer in China. Zhou Na,Zhang Chuan-Tao,Lv Hong-Ying,Hao Chen-Xing,Li Tian-Jun,Zhu Jing-Juan,Zhu Hua,Jiang Man,Liu Ke-Wei,Hou He-Lei,Liu Dong,Li Ai-Qin,Zhang Guo-Qing,Tian Zi-Bin,Zhang Xiao-Chun The oncologist BACKGROUND:IBM Watson for Oncology (WFO), which can use natural language processing to evaluate data in structured and unstructured formats, has begun to be used in China. It provides physicians with evidence-based treatment options and ranks them in three categories for treatment decision support. This study was designed to examine the concordance between the treatment recommendation proposed by WFO and actual clinical decisions by oncologists in our cancer center, which would reflect the differences of cancer treatment between China and the U.S. PATIENTS AND METHODS:Retrospective data from 362 patients with cancer were ingested into WFO from April 2017 to October 2017. WFO recommendations were provided in three categories: recommended, for consideration, and not recommended. Concordance was analyzed by comparing the treatment decisions proposed by WFO with those of the multidisciplinary tumor board. Concordance was achieved when the oncologists' treatment decisions were in the recommended or for consideration categories in WFO. RESULTS:Ovarian cancer showed the highest concordance, which was 96%. Lung cancer and breast cancer obtained a concordance of slightly above 80%. The concordance of rectal cancer was 74%, whereas colon cancer and cervical cancer showed the same concordance of 64%. In particular, the concordance of gastric cancer was very low, only 12%, and 88% of cases were under physicians choice. CONCLUSION:Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major cause of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. ClinicalTrials.gov Identifier: NCT03400514. IMPLICATIONS FOR PRACTICE:IBM Watson for Oncology (WFO) has begun to be used in China. In this study, concordance was examined between the treatment recommendation proposed by WFO and clinical decisions for 362 patients in our cancer center, which could reflect the differences of cancer treatment between China and the U.S. Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major causes of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. This study may have a significant effect on application of artificial intelligence systems in China. 10.1634/theoncologist.2018-0255

Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecologic oncology OBJECTIVE:To determine whether a non‑platinum chemotherapy doublet improves overall survival (OS) among patients with recurrent/metastatic cervical carcinoma. METHODS:Gynecologic Oncology Group protocol 240 is a phase 3, randomized, open-label, clinical trial that studied the efficacy of paclitaxel 175 mg/m plus topotecan 0.75 mg/m days 1-3 (n = 223) vs cisplatin 50 mg/m plus paclitaxel 135 or 175 mg/m (n = 229), in 452 patients with recurrent/metastatic cervical cancer. Each chemotherapy doublet was also studied with and without bevacizumab (15 mg/kg). Cycles were repeated every 21 days until progression, unacceptable toxicity, or complete response. The primary endpoints were OS and the frequency and severity of adverse effects. We report the final analysis of OS. RESULTS:At the protocol-specified final analysis, median OS was 16.3 (cisplatin-paclitaxel backbone) and 13.8 months (topotecan-paclitaxel backbone) (HR 1.12; 95% CI, 0.91-1.38; p = 0.28). Median OS for cisplatin-paclitaxel and topotecan-paclitaxel was 15 vs 12 months, respectively (HR 1.10; 95% CI,0.82-1.48; p = 0.52), and for cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab was 17.5 vs 16.2 months, respectively (HR 1.16; 95% CI, 0.86-1.56; p = 0.34). Among the 75% of patients in the study population previously exposed to platinum, median OS was 14.6 (cisplatin-paclitaxel backbone) vs 12.9 months (topotecan-paclitaxel backbone), respectively (HR 1.09; 95% CI, 0.86-1.38;p = 0.48). Post-progression survival was 7.9 (cisplatin-paclitaxel backbone) vs 8.1 months (topotecan-paclitaxel backbone) (HR 0.95; 95% CI, 0.75-1.19). Grade 4 hematologic toxicity was similar between chemotherapy backbones. CONCLUSIONS:Topotecan plus paclitaxel does not confer a survival benefit to women with recurrent/metastatic cervical cancer, even among platinum-exposed patients. Topotecan-paclitaxel should not be routinely recommended in this population. NCT00803062. 10.1016/j.ygyno.2023.01.010

Cervical Cancer in Sub-Saharan Africa: A Multinational Population-Based Cohort Study of Care and Guideline Adherence. Griesel Mirko,Seraphin Tobias P,Mezger Nikolaus C S,Hämmerl Lucia,Feuchtner Jana,Joko-Fru Walburga Yvonne,Sengayi-Muchengeti Mazvita,Liu Biying,Vuma Samukeliso,Korir Anne,Chesumbai Gladys C,Nambooze Sarah,Lorenzoni Cesaltina F,Akele-Akpo Marie-Thérèse,Ayemou Amalado,Traoré Cheick B,Wondemagegnehu Tigeneh,Wienke Andreas,Thomssen Christoph,Parkin Donald M,Jemal Ahmedin,Kantelhardt Eva J The oncologist BACKGROUND:Cervical cancer (CC) is the most common female cancer in many countries of sub-Saharan Africa (SSA). We assessed treatment guideline adherence and its association with overall survival (OS). METHODS:Our observational study covered nine population-based cancer registries in eight countries: Benin, Ethiopia, Ivory Coast, Kenya, Mali, Mozambique, Uganda, and Zimbabwe. Random samples of 44-125 patients diagnosed from 2010 to 2016 were selected in each. Cancer-directed therapy (CDT) was evaluated for degree of adherence to National Comprehensive Cancer Network (U.S.) Guidelines. RESULTS:Of 632 patients, 15.8% received CDT with curative potential: 5.2% guideline-adherent, 2.4% with minor deviations, and 8.2% with major deviations. CDT was not documented or was without curative potential in 22%; 15.7% were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease. Adherence was not assessed in 46.9% (no stage or follow-up documented, 11.9%, or records not traced, 35.1%). The largest share of guideline-adherent CDT was observed in Nairobi (49%) and the smallest in Maputo (4%). In patients with FIGO stage I-III disease (n = 190), minor and major guideline deviations were associated with impaired OS (hazard rate ratio [HRR], 1.73; 95% confidence interval [CI], 0.36-8.37; HRR, 1.97; CI, 0.59-6.56, respectively). CDT without curative potential (HRR, 3.88; CI, 1.19-12.71) and no CDT (HRR, 9.43; CI, 3.03-29.33) showed substantially worse survival. CONCLUSION:We found that only one in six patients with cervical cancer in SSA received CDT with curative potential. At least one-fifth and possibly up to two-thirds of women never accessed CDT, despite curable disease, resulting in impaired OS. Investments into more radiotherapy, chemotherapy, and surgical training could change the fatal outcomes of many patients. IMPLICATIONS FOR PRACTICE:Despite evidence-based interventions including guideline-adherent treatment for cervical cancer (CC), there is huge disparity in survival across the globe. This comprehensive multinational population-based registry study aimed to assess the status quo of presentation, treatment guideline adherence, and survival in eight countries. Patients across sub-Saharan Africa present in late stages, and treatment guideline adherence is remarkably low. Both factors were associated with unfavorable survival. This report warns about the inability of most women with cervical cancer in sub-Saharan Africa to access timely and high-quality diagnostic and treatment services, serving as guidance to institutions and policy makers. With regard to clinical practice, there might be cancer-directed treatment options that, although not fully guideline adherent, have relevant survival benefit. Others should perhaps not be chosen even under resource-constrained circumstances. 10.1002/onco.13718

Phase II Trial of MEDI0457 and Durvalumab for Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers. The oncologist BACKGROUND:Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers. METHODS:Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg intravenously every 4 weeks. The primary endpoint was overall response (RECIST 1.1). In this Simon two-stage phase 2 trial (Ho: p < 0.15; Ha: p ≥ 0.35), ≥2 responses were needed in both cervical and non-cervical cohorts during the first stage for the trial to proceed to stage 2 with an additional 25 patients (34 total) enrolled. RESULTS:Twenty-one patients (12 cervical, 7 anal, and 2 penile) were evaluable for toxicity and 19 for response Overall response rate was 21% (95% CI, 6%-46%) among evaluable patients. Disease control rate was 37% (95% CI, 16%-62%). Median duration of response among responders was 21.8 months (95% CI, 9.7%-not estimable). Median progression-free survival was 4.6 months (95% CI, 2.8%-7.2%). Median overall survival was 17.7 months (95% CI, 7.6%-not estimable). Grades 3-4 treatment-related adverse events occurred in 6 (23%) participants. CONCLUSIONS:The combination of MEDI0457 and durvalumab demonstrated acceptable safety and tolerability in patients with advanced HPV-16/18 cancers. The low ORR among patients with cervical cancer led to study discontinuation despite a clinically meaningful disease control rate. 10.1093/oncolo/oyad085