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Background: There is a strong rational of using anti-programmed cell death protein-1 and its ligand (anti-PD-1/L1) antibodies in human papillomavirus (HPV)-induced cancers. However, anti-PD-1/L1 as monotherapy induces a limited number of objective responses. The development of novel combinations in order to improve the clinical efficacy of an anti-PD-1/L1 is therefore of interest. Combining anti-PD-1/L1 therapy with an antitumor vaccine seems promising in HPV-positive (+) cancers. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (hTERT, human telomerase reverse transcriptase). UCPVax is being evaluated in a multicenter phase I/II study in NSCLC (non-small cell lung cancer) and has demonstrated to be safe and immunogenic. The aim of the VolATIL study is to evaluate the combination of atezolizumab (an anti-PD-L1) and UCPVax vaccine in a multicenter phase II study in patients with HPV+ cancers. Methods: Patients with HPV+ cancer (anal canal, head and neck, and cervical or vulvar), at locally advanced or metastatic stage, and refractory to at least one line of systemic chemotherapy are eligible. The primary end point is the objective response rate (ORR) at 4 months. Patients will receive atezolizumab every 3 weeks at a fixed dose of 1,200 mg in combination with the UCPVax vaccine at 1 mg subcutaneously. Discussion: Anti-cancer vaccines can restore cancer-immunity via the expansion and activation of tumor-specific T cells in patients lacking pre-existing anti-tumor responses. Moreover, preclinical data showed that specific TH1 CD4 T cells sustain the quality and homing of an antigen-specific CD8+ T-cell immunity. In previous clinical studies, the induction of anti-hTERT immunity was significantly correlated to survival in patients with advanced squamous anal cell carcinoma. Thus, there is a strong rational to combine an anti-cancer hTERT vaccine and an immune checkpoint inhibitor to activate and promote antitumor T-cell immunity. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a telomerase-based TH1 inducing vaccine (UCPVax) and an anti-PD-L1 (atezolizumab) immunotherapy in HPV+ cancers, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. [ABSTRACT FROM AUTHOR]

Background: There is a strong rational of using anti-programmed cell death protein-1 and its ligand (anti-PD-1/L1) antibodies in human papillomavirus (HPV)-induced cancers. However, anti-PD-1/L1 as monotherapy induces a limited number of objective responses. The development of novel combinations in order to improve the clinical efficacy of an anti-PD-1/L1 is therefore of interest. Combining anti-PD-1/L1 therapy with an antitumor vaccine seems promising in HPV-positive (+) cancers. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (hTERT, human telomerase reverse transcriptase). UCPVax is being evaluated in a multicenter phase I/II study in NSCLC (non-small cell lung cancer) and has demonstrated to be safe and immunogenic. The aim of the VolATIL study is to evaluate the combination of atezolizumab (an anti-PD-L1) and UCPVax vaccine in a multicenter phase II study in patients with HPV + cancers., Methods: Patients with HPV + cancer (anal canal, head and neck, and cervical or vulvar), at locally advanced or metastatic stage, and refractory to at least one line of systemic chemotherapy are eligible. The primary end point is the objective response rate (ORR) at 4 months. Patients will receive atezolizumab every 3 weeks at a fixed dose of 1,200 mg in combination with the UCPVax vaccine at 1 mg subcutaneously., Discussion: Anti-cancer vaccines can restore cancer-immunity via the expansion and activation of tumor-specific T cells in patients lacking pre-existing anti-tumor responses. Moreover, preclinical data showed that specific T H 1 CD4 T cells sustain the quality and homing of an antigen-specific CD8 + T-cell immunity. In previous clinical studies, the induction of anti-hTERT immunity was significantly correlated to survival in patients with advanced squamous anal cell carcinoma. Thus, there is a strong rational to combine an anti-cancer hTERT vaccine and an immune checkpoint inhibitor to activate and promote antitumor T-cell immunity. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a telomerase-based T H 1 inducing vaccine (UCPVax) and an anti-PD-L1 (atezolizumab) immunotherapy in HPV + cancers, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials., Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT03946358., Competing Interests: CB: Research grant from Bayer and Roche, advisory board for Bayer, Sanofi, MSD. FB: Novartis, Seagen, Daiichi Sankyo, Pierre Fabre, Astra-Zeneca, Clovis. SK: reports a consulting or advisory role for Ipsen, Incyte, Boehringer Ingelheim, Sanofi and BeiGene and has received research funding from Pfizer, Roche, Novartis, Bristol-Myers Squibb, Boehringer Ingelheim and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rebucci-Peixoto, Vienot, Adotevi, Jacquin, Ghiringhelli, de la Fouchardière, You, Maurina, Kalbacher, Bazan, Meynard, Clairet, Fagnoni-Legat, Spehner, Bouard, Vernerey, Meurisse, Kim, Borg and Mansi.)

Penile cancers are rare, the vast majority is represented by squamous cell carcinoma, with HPV virus being found in 30 to 40% of cases. At a locally advanced or metastatic stage, first-line treatment relies on platinum and taxane based polychemotherapy. The prognosis for advanced or metastatic penile cancer remains poor, with overall survival ranging from 13.9 to 17.1 months. After the first line, guidelines recommend various chemotherapy treatments or targeted anti-EGFR therapies whose results as well as the level of evidence are limited. A better understanding of the oncogenic pathways involved in penile cancer and a frequent expression of PD-L1 are the rationale for the elaboration of new strategies. This review article presents the data, guidelines and ongoing studies in locally advanced or metastatic penile cancer., (Copyright © 2020 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)

Castration resistant prostate cancer occurs when patients experience disease progression despite appropriate hormonal manipulations. In these patients, chemotherapy remains standard treatment. Preclinical and clinical data have demonstrated the potential utility of an immunotherapy-based approach for the treatment of prostate cancer (PC). The phase III trial (IMPACT) has recently reported an advantage for Sipuleucel-T over placebo, with an overall survival 4.1 months superior to placebo. Sipuleucel-T is also the first FDA-approved immunotherapy for prostate cancer. These promising results need to be confirmed with other large studies and within previous step of PC. Neoplasic cells can escape immune responses by multiple mechanisms. A better knowledge of these mechanisms is of major concern for the future development of new immunotherapies approach.

Breast cancer incidence remains the highest among gynaecologic neoplasms. Once they have achieved their treatments, patients should undergo careful follow-up. It aims at detecting early local recurrence or controlateral breast cancer. Based on large cohorts, clinical and radiological follow-up procedures come from guidelines realised by scientific organisations. We evaluated our regional practices in Franche-Comté and compared them to current guidelines. Patients with early breast cancer positive for hormonal receptors filled a questionnaire concerning their follow-up. It included patients treated from 1999 to 2005. When frequency of consultation is evaluated, only half of the patients undergo what is recommended. Whereas mammography and non-validated complementary exams are more regularly realised. Patients consulting more one practician have a better compliance. Our study underlines significant disparities among patients follow-up. Better interactions between physicians and a greater implication of patients in their follow-up would increase its quality.

The pemetrexed disodium (Alimta), LY231514) is the first antifolate able to inhibit at the same time the synthesis of purins and pyrimidins. Many therapeutic tests were carried out in clinical situations where the methotrexate and the fluorouracil had been the proof of their effectiveness. It then showed an interesting activity in a great number of tumours but with very different profiles of tolerance according to the studies and pathologies. The explanation will come in 2001 by the description from the relation between the vitamin deficiencies among treated patients and occurred from toxicities. The two randomized studies carried out in the malignant pleural mesothelioma and the non small cell lung cancer made it possible to establish its utility and to record the pemetrexed in these clinical situations. Others axes of development remain possible, but the results are stanby or to confirm as in squamous-cell cancer in the head and neck and breast, digestive or urinary tracts cancer. In all the cases, the optimization of the pemetrexed in terms of amount/methods of administration and associations possible because of its profile of tolerance makes of it a molecule of chemotherapy with a future.