Society of Gynecologic Oncology Journal Club: Controversial conversations in Gynecologic cancer - The ABCs of ADCs (Antibody drug Conjugates).

The Society of Gynecologic Oncology (SGO) Journal Club is held quarterly to discuss topics related to gynecological malignancies. On November 8, 2022, the SGO Journal Club focused on antibody-drug conjugates (ADCs) in gynecologic malignancies, including the pharmacology, toxicities, and results of recent clinical trials leading to FDA approval of two new therapies for cervical and ovarian cancer. The invited discussants included Drs. Erin Hickey Zacholski, Roisin O'Cearbhaill, and Ursula Matulonis who discussed the pharmacology of ADCs, GOG-3023/ENGOT-cx6 (Coleman et al., 2021 May) and the SORAYA study (Ursula Matulonis, Domenica Lorusso, Ana Oaknin, Sandro Pignata, Hannelore Denys, Nicoletta Colombo, Toon Van Gorp, Jason Konner, Margarita Romeo Marin, Philipp Harter, Conleth Murphy, Jiuzhou Wang, Elizabeth Noble, Brooke Esteves, Michael Method, Robert Coleman, Efficacy and Safety of Mirvetuximab Soravtansine in Patients with Platinum-Resistant Ovarian Cancer with High Folate Receptor Alpha Expression: Results from the SORAYA Study (LBA 4), Gynecologic Oncology, Volume 166, Supplement 1, ,2022).

Exploiting somatic alterations as therapeutic targets in advanced and metastatic cervical cancer.

It is estimated that 604,127 patients were diagnosed with cervical cancer worldwide in 2020. While a small percentage of patients will have metastatic disease at diagnosis, a large percentage (15-61%) later develop advanced disease. For this cohort, treatment with systemic chemotherapy remains the standard of care, with a static 5-year survival rate over the last thirty years. Data on targetable molecular alterations in cervical cancer have lagged behind other more common tumor types thus stunting the development of targeted agents. In recent years, tumor genomic testing has been increasingly incorporated into our clinical practice, opening the door for a potential new era of personalized treatment for advanced cervical cancer. The interim results from the NCI-MATCH study reported an actionability rate of 28.4% for the cervical cancer cohort, suggesting a subset of patients may harbor mutations which that are targetable. This review sets out to summarize the key targeted agents currently under exploration either alone or in combination with existing treatments for cervical cancer.

Adjuvant chemotherapy in patients with stage I endometrioid or clear cell ovarian cancer in the platinum era: a Surveillance, Epidemiology, and End Results Cohort Study, 2000-2013.

BACKGROUND: We sought to evaluate the impact of adjuvant chemotherapy on overall survival (OS) in patients with stage I endometrioid epithelial ovarian cancer (EEOC) or ovarian clear cell cancer (OCCC) using a national database. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I EEOC or OCCC from 2000 to 2013. We sought to identify predictors of chemotherapy use and to assess the impact of chemotherapy on OS in these patients. OS was compared using the log-rank test and the Cox proportional hazards model. RESULTS: In all, 3552 patients with FIGO stage I EEOC and 1995 patients with stage I OCCC were identified. Of the 1600 patients (45%) with EEOC who underwent adjuvant chemotherapy, the 5-year OS rate was 90%, compared with 89% for those who did not undergo adjuvant chemotherapy (P = 0.807). Of the 1374 (69%) patients with OCCC who underwent adjuvant chemotherapy, the 5-year OS rate was 85%, compared with 83% (P = 0.439) for those who did not undergo adjuvant chemotherapy. Chemotherapy use was associated with younger age, higher substage, and more recent year of diagnosis for both the EEOC and OCCC groups. Only in the subgroup of patients with FIGO substage IC, grade 3 EEOC (n = 282) was chemotherapy associated with an improved 5-year OS-81% compared with 62% (P = 0.003) in untreated patients (HR: 0.583; 95% CI: 0.359-0.949; P = 0.030). In patients with OCCC, there was no significant effect of adjuvant chemotherapy on OS in any substage. CONCLUSIONS: Adjuvant chemotherapy was associated with improved OS only in patients with substage IC, grade 3 EEOC. In stage I OCCC, adjuvant chemotherapy was not associated with improved OS.

Evaluation of carboplatin dosage based on 4-variable modification of diet in renal disease equation.

BACKGROUND: Traditionally, carboplatin dosage is based on the Calvert formula. Glomerular filtration rate (GFR) and creatinine clearance (CrCl) are often used interchangeably in this formula. The modification of diet in renal disease (MDRD) equation is now routinely available to estimate GFR (eGFR). METHODS: We performed a retrospective analysis of carboplatin dosage in our institute. Calvert formula derived carboplatin dose using eGFR calculated from the MDRD equation was compared to estimated CrCl from the Cockcroft-Gault and Jelliffe equations. RESULTS: Ninety-two carboplatin treatment episodes were recorded. eGFR and CrCl correlated reasonably well with a correlation coefficient (r) of 0.88. The correlation was weakest at lower levels of serum creatinine. Correcting eGFR for body surface area resulted in a tighter correlation (r = 0.94). CONCLUSION: The MDRD derived eGFR is readily available and may prove very useful in calculating carboplatin dosage for patients with impaired renal function.