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Simple Summary: Randomized clinical trials show a survival benefit associated with immuno-molecular therapy (IMT) use in metastatic or recurrent cervical cancer. This study investigated IMT use and survival in stage IVB cervical cancer patients in Commission on Cancer® (CoC)®-accredited facilities. Patients diagnosed with stage IVB cervical cancer in the National Cancer Database and treated with first-line therapy with chemotherapy alone or with radiotherapy ± IMT were studied. Adjusted risks of death were estimated in patients treated with ±IMT after applying a propensity score analysis to balance the clinical covariates. There were 3164 evaluable patients, including 31% who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. In propensity-score-balanced patients, the median survival was 5 months longer with vs. without IMT. The adjusted risk of death was 28% lower following treatment with vs. without IMT. IMT was associated with a consistent survival benefit in real-world patients in (CoC)®-accredited facilities with stage IVB cervical cancer. Purpose: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. Methods: Patients diagnosed with stage IVB cervical cancer during 2013–2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. Results: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64–0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. Conclusions: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: For a few years, lenalidomide plus dexamethasone (Len/Dex) has become a new standard of care for newly diagnosed multiple myeloma (NDMM) patients who are not eligible for autologous stem cell transplantation. The FIRST trial showed that continuous therapy with Len/Dex is superior in progression-free survival (PFS) and overall survival (OS) compared to fixed treatment or triplet, leading to approval for NDMM. The knowledge of the safety and efficacy of Len/Dex in frail and ultra-frail patients is limited. This study evaluates the Len/Dex combination, correlating it with the prognostic impact of different variables on PFS and OS. Our real-world data report that an elderly and frail population, rarely included in randomized clinical trials, may benefit from Len/Dex combination, with an incidence of adverse events that is inferior to pivotal trials. Thus, the oral and self-administering outpatient Len/Dex scheme is a considerable treatment choice in patients with high ECOG or age >75 years old. Based on the results obtained in clinical trials, the use of the combination of lenalidomide and dexamethasone (Len/Dex) has become a potential therapeutic choice for newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation. This study evaluated 89 frail NDMM patients treated with first-line oral association. At the last follow-up, 34 out of 89 patients (38.2%) were alive, and 22 were still in treatment with Len/Dex. Among 73 evaluable patients who received at least two cycles, the overall response rate was 71% (N = 52). The disease control rate, defined as any level of clinical response to therapy, occurred in 71 patients (97%). We reported one or more adverse events of grade 3 or 4 (G3/4) in 65.2% (N = 58) of patients, with a prevalence of hematological toxicity (24 patients), leading to an overall discontinuation of treatment in two cases. In univariate analysis, high ISS, high serum β2-microglobulin, and creatinine clearance <30 mL/min negatively impact OS, while the depth of response positively impacts OS. Moreover, G3-4 anemia, ISS, frailty score, and ECOG negatively impacts PFS. In conclusion, elderly and more frail patients benefit from the Len/Dex combination also in the era of monoclonal antibodies, ensuring an increased PFS and OS in patients where the therapeutic choice is often limited and usually not very effective. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy-based combinations represent the front-line standard of care for metastatic clear cell renal cell carcinoma (mccRCC) patients. These combinations lead to an overall survival improvement and a dramatic increase of complete response rate raising the question of possible cure of mccRCC patients. This review summarizes the recent advances in RCC treatment and biological aspects underpinning a possible healing. Renal-cell carcinoma (RCC) accounts for 2% of cancer diagnoses and deaths worldwide. Clear-cell RCCs represent the vast majority (85%) of kidney cancers and are considered morphologically and genetically as immunogenic tumors. Indeed, the RCC tumoral microenvironment comprises T cells and myeloid cells in an immunosuppressive state, providing an opportunity to restore their activity through immunotherapy. Standard first-line systemic treatment for metastatic patients includes immune-checkpoint inhibitors (ICIs) targeting PD1, in combination with either another ICI or with antiangiogenic targeted therapy. During the past few years, several combinations have been approved with an overall survival benefit and overall response rate that depend on the combination. Interestingly, some patients achieve prolonged complete responses, raising the question of whether these metastatic RCC patients can be cured. This review will focus on recent therapeutic advances in RCC and the clinical and biological aspects underpinning the potential for healing. [ABSTRACT FROM AUTHOR]

Simple Summary: First-line treatment options for metastatic clear cell renal cell carcinoma have significantly increased. The current recommended therapeutic strategy is based on a combination, but monotherapy remains an alternative. However, the choice of the type of combination, i.e., dual immunotherapy or immunotherapy combined with an antiangiogenic drug, has not been clearly standardized. A strategy based on the International Metastatic Database Consortium (IMDC) classification is currently recommended with pembrolizumab + axitinib, cabozantinib + nivolumab, and lenvatinib + pembrolizumab (for all patients) or nivolumab + ipilimumab (for patients with intermediate or poor risk), which are the first-line treatment standards of care. This review summarizes all recent data from the main combinations evaluated in first-line treatment and discusses the choice of drugs according to the patient's profile and the benefit/risk balances of each combination. The development of antiangiogenic treatments, followed by immune checkpoint inhibitors (ICI), has significantly changed the management of metastatic clear cell renal cell cancer. Several phase III trials show the superiority of combination therapy, dual immunotherapy (ICI-ICI) or ICI plus tyrosine kinase inhibitors (TKI) of the vascular endothelium growth factor (VEGF) over sunitinib monotherapy. The question is therefore what is the best combination for a given patient? A strategy based on the International Metastatic Database Consortium (IMDC) classification is currently recommended with pembrolizumab + axitinib, cabozantinib + nivolumab, and lenvatinib + pembrolizumab (for all patients) or nivolumab + ipilimumab (for patients with intermediate or poor risk), which are the first-line treatment standards of care. However, several issues remain unresolved and require further investigation, such as the PD-L1 status, the relevance of possible options based on the patient's profile, and consideration of second-line and subsequent treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: The expected change in overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) after the clinical implementation of immune checkpoint inhibitor therapy (ICI) has not been substantially investigated in large real-world cohorts outside randomized controlled trials (RCTs). In this nationwide study, we compared OS before and after the implementation of ICI and found that 3-year OS tripled from 6% to 18%. Patients receiving ICI had a lower OS than demonstrated in RCTs, except for patients with performance status (PS) 0. More than a fifth of the patients progressed early within the first six ICI cycles. Adverse prognostic factors were PS ≥ 1 and metastases to the bone and liver. Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6–20.0) and 6% (95% CI 5.1–7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has made a breakthrough in the treatment of patients with recurrent and/or metastatic head and neck squamous cell carcinoma in the second line setting with anti-PD-1/PD-L1 immune checkpoint inhibitors. Furthermore, the KEYNOTE-048 study has established a new standard of care with immunotherapy in the first line setting, leading to a paradigm change for the treatment of patients with recurrent and/or metastatic head and neck squamous cell carcinoma. No study since 2008 could demonstrate an improvement in survival of these patients until the publication of the KEYNOTE-048 study. Here we will decipher this new paradigm in the first-line line setting and discuss associated challenges. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) in combination with platinum-based chemotherapy has been for the decade standard of care for the treatment of head and neck squamous cell carcinomas (HNSCC) patients in the first-line recurrent and/or metastatic setting. The KEYNOTE-048 trial published last year established a new paradigm in this setting with the demonstration that immunotherapy should be given either alone or in combination with chemotherapy. Indeed, pembrolizumab, an antiprogrammed cell death 1 (PD-1) immune checkpoint inhibitor, improved overall survival as compared to the EXTREME regimen in patients expressing PD-L1 in the tumor microenvironment, which represents a large majority of the patient population. In this review, we will decipher this important change of paradigm in the first-line treatment of recurrent and/or metastatic HNSCC, and discuss associated challenges. [ABSTRACT FROM AUTHOR]

Clinical outcomes of chemotherapy for patients with advanced pancreatic adenocarcinoma in a real-world setting might differ from outcomes in randomized clinical trials (RCTs). Here we show in a single-institution cohort of 595 patients that median overall survival (OS) of patients who received gemcitabine alone (n = 185; 6.6 months (95% CI; 5.5–7.7)) was the same as in pivotal RCTs. Gemcitabine/capecitabine (n = 60; 10.6 months (95% CI; 7.8–13.3)) and gemcitabine/nab-paclitaxel (n = 66; 9.8 months (95% CI; 7.9–11.8)) resulted in a longer median OS and fluorouracil/oxaliplatin/irinotecan (n = 31, 9.9 months (95% CI; 8.1–11.7)) resulted in a shorter median OS than previously reported. Fluorouracil/oxaliplatin (n = 35, 5.8 months (95% CI; 4.5–7)) and best supportive care (n = 206, 1.8 months (95% CI; 1.5–2.1)) could not be benchmarked against any RCTs. The degree of protocol adherence explained differences between real-world outcomes and the respective RCTs, while exposure to second-line treatments did not. [ABSTRACT FROM AUTHOR]