The Effect of Previous Pregnancies in Patients With Gynecological Neoplasms Treated With PD-1/PD-L1 Inhibitors

NCT06945601 | Not Yet Recruiting

• 1 other identifier: FECONDE
• Study Type: observational
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

Despite the fact that immunotherapy has radically changed the therapeutic landscape in multiple types of tumors, to date the only predictive factor for response to treatment with immune checkpoint inhibitors (ICI), although with many limitations and very different specificity among different pathologies, remains the expression of PD-L1. Several meta- analyses of randomized studies have shown that the female sex is associated with less benefit compared to the male sex in patients with melanoma and NSCLC. Reviewing the available data in the literature, this reduced efficacy is confirmed only in the mono- immunotherapy settings, while when chemo-immune combinations are administered, women seem to benefit more than men. Pregnancy, being associated with immunological changes that can last over time (e.g., mechanisms of immuno-tolerance, antigen sharing between the placenta and neoplasia, fetal microchimeric cells, etc.), could partly explain the impact of sex on the outcome of immune checkpoint inhibitors. In particular, some mechanisms of immunotolerance, such as the increase of T-regulatory cells specific to oncofetal antigens in the endometrium, could potentially suggest a lower efficacy of immunotherapy in women. The current study, by characterizing the impact of previous pregnancies on oncological outcomes, could contribute to providing the basis for future research aimed at defining the biological mechanisms underlying the effect of pregnancy on the immune system and the efficacy of immune checkpoint inhibitors. The study has an observational, retrospective/prospective, multicenter design. Female patients with endometrial and cervical cancer will be included. All these patients will be treated with ICIs either as monotherapy or in combination with chemo-immunotherapy. Clinical and oncological anamnesis information will be collected for each patient (type of neoplasm, line of therapy, age at the start of therapy, weight, height, smoking habits, comorbidities, performance status, number and site of metastases, concomitant non- oncological therapies); anatomical-pathological parameters will also be collected (level of PD-L1 expression, molecular and mutational profile of the tumor). Additionally, information regarding the woman's pregnancy and fertility history will be gathered (age at menarche/menopause, number of pregnancies, age at first pregnancy, age at last pregnancy, any HRT or contraceptive therapy, any gynecological surgery).

Conditions

Gynecologic Cancers

Outcome Measures

Primary Outcomes (1)

• Difference of PFS between the cohorts

  Progression-Free Survival (PFS) is defined as the interval between the start of therapy and the radiological evidence of disease progression or death.

  The analysis of the primary endpoint will be performed when approximately 75-80% of patients have experienced the event of interest (disease progression or death). Through study completion, an average of 5 years.

Secondary Outcomes (1)

• Difference of OS and the RR between the cohorts

  The analysis of the secondary endpoints will be conducted following the analysis of the primary endpoint. Through study completion, an average of 5 years.

Study Arms (4)

Cervical Cancer (K cervix) with pregnancy

Patients with cervical cancer (k cervix) with one or more previous pregnancies

Drug: ICI monotherapy or combinations of chemo- immunotherapy

Endometrial Cancer (K endometrium) with pregnancy

Patients with endometrial cancer (K endometrium) with one or more previous pregnancies

Drug: ICI monotherapy or combinations of chemo- immunotherapy

Cervical Cancer (K cervix)

Patients with cervical cancer (K cervix)

Drug: ICI monotherapy or combinations of chemo- immunotherapy

Endometrial Cancer (K endometrium)

Patients with endometrial cancer (K endometrium)

Drug: ICI monotherapy or combinations of chemo- immunotherapy

Interventions

ICI monotherapy or combinations of chemo- immunotherapy DRUG

ICI monotherapy or combinations of chemo- immunotherapy

Also known as: immunotherapy, combination of chemotherapy with immunotherapy, PD-1/PD-L1 inhibitors, immunotherapy, chemotherapy, immune checkpoint inhibitors

Cervical Cancer (K cervix); Cervical Cancer (K cervix) with pregnancy; Endometrial Cancer (K endometrium); Endometrial Cancer (K endometrium) with pregnancy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Female patients of all ages, 18 years and older, with endometrial or cervical cancer who have received or will receive treatment with ICI monotherapy or combinations of chemo- immunotherapy will be included.

You may qualify if:

• For patients past-pregnant and nulliparous:
• Age 18 years or older
• Female sex
• Confirmed cytological/histological diagnosis of endometrial or cervical cancer
• Treatment with ICI monotherapy or in combination with chemotherapy
• Written informed consent for living patients Only for patients past-pregnant:
• Available obstetric history

You may not qualify if:

• Not eligible for treatment with ICI either in monotherapy or in combination with chemotherapy.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

MeSH Terms

Interventions

Immunotherapy; Immune Checkpoint Inhibitors; Drug Therapy

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. Specialist in Medical Oncology

Study Record Dates

• First Submitted: April 10, 2025
• First Posted: April 25, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030
• Last Updated: April 25, 2025

Record last verified: 2025-04