Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial

Accinno, Valentina; Altavilla, Chiara; Andreetta, Claudia; Antonelli, Giovanna; Arenare, Laura; Artioli, Grazia; Avola, Francesco; Barbara, Bonifacio; Barbato, Valentina; Bartoletti, Michele; Bevilacqua, Simona; Bordonaro, Roberto; Borghese, Oriana; Buonfanti, Gaetano; Califano, Daniela; Camarda, Floriana; Canzanella, Giuliana; Carbone, Maria Rita; Stella, Giulia Carlo; Casanova, Cláudia; Cassani, Chiara; Castagna, Fabrizio; Cattaneo, Monica; Cecere, Sabrina Chiara; Chiodini, Paolo; Cinefra, M.; Cinieri, Saverio; Colombo, Nicoletta; Corsetti, Serena; Dall’Agata, Monia; D’Amico, Maria Rosaria; Daniele, Gennaro; Angelis, Carmine De; Cecio, Rossella De; Giorgi, Ugo De; Marino, Elvira De; Matteis, Giovanni De; Placido, Sabino De; Bene, Gabriella Del; Giudice, Antonia Del; Monte, Francesca Del; Sesto, Michele Del; Napoli, Marilena Di; Donini, Maddalena; Drudi, G.; Falcone, G; Farolfi, Alberto; Favaretto, Adolfo; Ferrera, Giulia; Florio, Manuela; Forestieri, Valeria; Gallo, Marianna; Gallo, Ciro; Gargiulo, Piera; Garibaldi, Francesca; Gerevini, Fabiana; Ghizzoni, Viola; Giganti, Maria Olga; Gimigliano, Anna; Giudice, Elena; Gnocchi, Nicoletta; Gravina, Adriano; Greco, Filippo; Greggi, Stefano; Iaia, Maria Laura; Ilardi, Annalisa; Iovine, Gelsomina; Ippoliti, Gabriella; Irollo, Giulia; Isidori, Ilenia; Lapresa, Mariateresa; Lavenia, G.; Lombardi, Davide; Longhitano, Laura; Lorusso, Domenica; Lucia, Bortot; Luzi, Gabriella; Mammoliti, Serafina; Mariano, Sara; Marino, Valentina; Marrapese, Giovanna; Martino, Marilena; Matocci, Roberta; Mazzoni, E.; Mercuri, Daniela; Mirto, Maria; Mollo, Giovanna; Montinaro, A.; Moscatelli, Marta; Mosconi, Anna Maria; Musacchio, Lucia; Nanni, Nicoletta; Natalucci, Pamela; Nicoloso, Milena S.; Orditura, Michele; Parma, Gabriella Maria; Passalacqua, Rodolfo; Pelone, Michela; Perri, Maria Teresa; Perrone, Francesco; Perrucci, Bruno; Piancastelli, A; Piccirillo, Maria Carmela; Piccolo, Antonio; Pignata, Sandro; Pisano, Carmela; Priolo, Domenico; Rapisardi, Stefania; Ravaglia, Giorgia; Ribecco, Teresa; Ricci, Caterina; Roccio, Marianna; Romano, Fiorella; Rosati, Marta; Russo, Daniela; Salutari, Vanda; Sambataro, Daniela; Savio, Alfonso; Scaffa, Cono; Scalone, Simona; Scambia, Giovanni; Schettino, Clorinda; Schiavetto, Ilaria; Sergi, Concetta; Sgandurra, Francesca; Sorio, Roberto; Spina, Anna; Stabile, Stefano; Tabaro, Gianna; Tambaro, Margherita; Tamberi, Stefano; Tecchiato, Angelica; Trujillo, Ángela Maria; Zaccarelli, Eleonora; Zafarana, Elena

doi:10.1016/s1470-2045(23)00016-5

Cited by 13 publications

(7 citation statements)

References 23 publications

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“…138 In addition, Asian, Black, and Hispanic people are less likely to receive recommended germline genetic testing necessary for the receipt of game-changing treatments, 139 such as the immunotherapy that has been shown to extend progression-free 24-month survival by threefold for patients with advanced mismatch-repair-deficient endometrial cancer. 104 Five-year relative cancer survival is lower among Black people (67%) than among White people (72%) even when socioeconomic status is high, 130 and Black children are 24% more likely to be diagnosed with distant-stage childhood cancer than White children, regardless of family insurance status. 140 The economic burden of racial and ethnic health inequalities was recently estimated at $421-$451 billion in 2018, mostly because of the poor health of Black individuals.…”

Section: Cancer Disparities By Race and Ethnicitymentioning

confidence: 99%

Cancer statistics, 2024

Siegel,

Giaquinto,

Jemal

2024

CA A Cancer J Clinicians

1,099

155

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Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population‐based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2020) and mortality data collected by the National Center for Health Statistics (through 2021). In 2024, 2,001,140 new cancer cases and 611,720 cancer deaths are projected to occur in the United States. Cancer mortality continued to decline through 2021, averting over 4 million deaths since 1991 because of reductions in smoking, earlier detection for some cancers, and improved treatment options in both the adjuvant and metastatic settings. However, these gains are threatened by increasing incidence for 6 of the top 10 cancers. Incidence rates increased during 2015–2019 by 0.6%–1% annually for breast, pancreas, and uterine corpus cancers and by 2%–3% annually for prostate, liver (female), kidney, and human papillomavirus‐associated oral cancers and for melanoma. Incidence rates also increased by 1%–2% annually for cervical (ages 30–44 years) and colorectal cancers (ages <55 years) in young adults. Colorectal cancer was the fourth‐leading cause of cancer death in both men and women younger than 50 years in the late‐1990s but is now first in men and second in women. Progress is also hampered by wide persistent cancer disparities; compared to White people, mortality rates are two‐fold higher for prostate, stomach and uterine corpus cancers in Black people and for liver, stomach, and kidney cancers in Native American people. Continued national progress will require increased investment in cancer prevention and access to equitable treatment, especially among American Indian and Alaska Native and Black individuals.

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Section: Cancer Disparities By Race and Ethnicitymentioning

confidence: 99%

Cancer statistics, 2024

Siegel,

Giaquinto,

Jemal

2024

CA A Cancer J Clinicians

1,099

155

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show abstract

“…After the removal of duplicate records, and the assessment of the studies based on title and abstract, 2,193 references were excluded and 41 full-text manuscripts were eligible and thoroughly reviewed for inclusion and exclusion criteria. Of these, three clinical trials in 41 references satisfied the eligibility criteria and formed the scope of the analysis, comprising 1,431 patients [ 29 – 31 ].…”

Section: Resultsmentioning

confidence: 99%

“…We performed a leave-one-out sensitivity analysis for all outcomes. There was no significant difference in the OS at 24 months in patients with dMMR tumors omitting MITO END-3 or RUBY trials [ 30 , 31 ]. There was no significant difference in the OS at 30 months in patients with dMMR tumors omitting MITO END-3 or NRG-GY018 trials [ 29 , 31 ].…”

Section: Resultsmentioning

confidence: 99%

“…There was no significant difference in the OS at 24 months in patients with dMMR tumors omitting MITO END-3 or RUBY trials [ 30 , 31 ]. There was no significant difference in the OS at 30 months in patients with dMMR tumors omitting MITO END-3 or NRG-GY018 trials [ 29 , 31 ]. There was no significant difference in the PFS at 30 months in patients with dMMR tumors omitting NRG-GY018 trial [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

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PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer: a systematic review and meta-analysis of randomized clinical trials

de Moraes,

Pasqualotto,

Lopes

et al. 2023

BMC Cancer

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Background Paclitaxel and carboplatin is the standard chemotherapy for the treatment of advanced or recurrent endometrial cancer. However, the benefit of adding programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors to chemotherapy is still unclear. Method We searched PubMed, Scopus, Cochrane, and Web of Science databases for randomized controlled trials that investigated PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer. We computed hazard ratios (HRs) or risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses. Results A total of three studies and 1,431 patients were included. Compared with carboplatin plus paclitaxel-based chemotherapy, progression-free survival (PFS) rate (HR 0.32; 95% CI 0.23–0.44; p < 0.001) and overall survival (OS) at 30 months (RR 3.13; 95% CI 1.26–7.78; p = 0.01) were significant in favor of the PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel group in the mismatch repair–deficient subgroup. However, there were no significant differences in the mismatch repair–proficient subgroup for PFS (HR 0.74; 95% CI 0.50–1.08; p = 0.117) or OS at 30 months (RR 2.24; 95% CI 0.79–6.39; p = 0.13). Conclusion Immunotherapy plus carboplatin-paclitaxel increased significantly PFS and OS among patients with advanced or recurrent endometrial cancer, with a significant benefit in the mismatch repair–deficient and high microsatellite instability population.

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“…MITO END-3 is a randomized phase 2 trial comparing PC with carboplatin, paclitaxel, and avelumab in treating advanced (stage III-IV) or recurrent endometrial cancer, which showed results comparable to those observed in the DUO-E and AtTEnd trials [ 5 ].…”

Section: Endometrial Cancermentioning

confidence: 99%

Major clinical research advances in gynecologic cancer in 2023: a tumultuous year for endometrial cancer

Shim,

Lee,

Lee

et al. 2024

J Gynecol Oncol

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In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.

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Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial

Cited by 13 publications

References 23 publications

Cancer statistics, 2024

Cancer statistics, 2024

PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer: a systematic review and meta-analysis of randomized clinical trials

Major clinical research advances in gynecologic cancer in 2023: a tumultuous year for endometrial cancer

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