David O'Malley, MD, professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine, and director of the Division of Gynecologic Oncology at The Ohio State University Comprehensive Cancer Center–The James, discusses the role of PARP inhibitors in the treatment landscape of ovarian cancer.

We now know there is a group of patients who will benefit remarkably from the use of PARP inhibitors, and that includes patients who have either a BRCA1 or BRCA2 mutation, says O’Malley. Whenever a survival advantage is seen, we know it is going to be beneficial. It is clear now that this group of patients with BRCA1/2-mutant ovarian cancer will benefit from PARP inhibitors, and they should receive these therapies earlier on.

There are 3 PARP inhibitors now available in the treatment landscape for ovarian cancer, with the most recent approval of niraparib (Zejula) in the frontline setting for adult patients who are in a complete or partial response to first-line platinum-based chemotherapy. According to O’Malley, PARP inhibitors should be given in the frontline setting for patients harboring a BRCA1/2 mutation, but if they do not receive it in their first-line of therapy and receive a platinum instead, they should be receiving a PARP inhibitor in the platinum-sensitive, recurrent setting.

<< View more resources and information in ovarian cancer

Videos

David O'Malley, MD, discusses the role of PARP inhibitors in the treatment landscape of ovarian cancer.

PARP Inhibition Improves Outcomes in Patients With BRCA-Mutated Ovarian Cancer

A 68-Year-Old Woman With Stage IV Ovarian Cancer

Molecular Testing in Newly Diagnosed Patients

Frontline Therapy Options for Stage IV Ovarian Cancer

GOG-0218 and ICON7 Trial Regimens as Maintenance Therapy

Maintenance Therapy: NCCN Guidelines, PAOLA-1 Trial

Emerging Frontline and I/O PARP Combination Therapies

The Direction of Ovarian Cancer Management

A 68-year-old postmenopausal woman presented with fatigue, urinary frequency, early satiety, abdominal bloating and distention

PMH: HTN, medically treated with lisinopril

SH: retired; grandmother of 3; never-smoker; social alcohol use

PE: abdominal distention, bloating, and a positive fluid wave test; otherwise unremarkable

Pelvic exam with transvaginal ultrasound showed a right ovarian mass

Chest/abdomen/pelvis CT with contrast revealed a right adnexal 5.3-cm complex mass, a suspicious intraparenchymal liver lesion, retroperitoneal lymph node enlargement and concurrent pleural effusion

Lymph node and adnexal mass biopsy confirmed high-grade, epithelial ovarian cancer; positive cytology of pleural effusion

Patient underwent TAH/BSO, lymph node dissection, with suboptimal debulking; residual disease 1.3 cm

Paclitaxel/carboplatin/bevacizumab + maintenance bevacizumab

After 3 cycles, patient underwent second debulking surgery, R0

Continued on bevacizumab for 6 more cycles

Achieved partial response, post treatment CA-125, 40 U/mL
 

Chest/abdomen/pelvis CT showed no gross pelvic masses or nodes

Ramez Eskander, MD, presents the case of a 68-year-old woman with stage IV ovarian cancer, and discusses the management approach for this patient and similar cases. 

Brian M. Slomovitz, MD, professor and chief in the Division of Gynecologic Oncology at the Sylvester Comprehensive Cancer, University of Miami Health System, discusses the some of the subcategories of endometrial cancer and how the make a difference for patients’ treatment.

Patients with endometrial cancer, more so than those with any other gynecological cancer, can fall into 1 of 4 subgroups as defined by the Cancer Genome Atlas (TCGA) Program. Slomovitz says that based on where a patients’ disease lies in terms of these subgroups, there are different outcomes as well as different treatment options. Patients with a mutated profile, high microsatellite instability, or mismatch repair deficiency are more amenable and more likely to respond to immunotherapy.

At the PER 11th Annual International Symposium on Ovarian Cancer and Other Gynecologic Malignancies, Slomovitz discussed biologic therapies and his study on mTOR inhibition in combination with hormonal therapy for these patients. Particularly in patients who were chemotherapy-naïve, he and his fellow investigators saw a high response rate and a longer progression-free survival. He thinks that physicians in this setting should take advantage of these response and survival rates by giving biological therapy sooner and holding the chemotherapy for later lines of treatment.

<< View more resources and information in endometrial cancer

Brian M. Slomovitz, MD, discusses the some of the subcategories of endometrial cancer and how the make a difference for patients’ treatment.

How Different Factors Affect Treatment of Endometrial Cancer

Yousef Zakharia, MD, clinical associate professor of internal medicine at the University of Iowa, Holden Comprehensive Cancer Center, discusses the next steps after the phase 1 trial (NCT02535533) of seleno-L-methionine (SLM) in combination with axitinib (Inlyta) as treatment of adult patients with previously treated or relapsed clear cell renal cell carcinoma (ccRCC).

Zakharia says that 1 of the observations they had while investigating this clinical trial was that the higher the blood concentration was with SLM, the better response patients had. Although this was a small cohort of patients, the investigators amended the protocol in the study to allow patients with ccRCC to be treated based on their body surface area, and this topic is still ongoing among the authors.

If they continue to see efficacy in the phase 1 data, the next step will be to start a randomized clinical trial of axitinib as the standard of care and the combination of axitinib and SLM in patients with advanced metastatic ccRCC, according to Zakharia.

<< View more resources and information regarding renal cell carcinoma

Yousef Zakharia, MD, discusses the next steps after the phase 1 trial of seleno-L-methionine in combination with axitinib as treatment of adult patients with previously treated or relapsed clear cell renal cell carcinoma.

Evaluating Future Steps for Investigating Seleno-L-Methionine in RCC

Winston Tan, MD, consultant, Division of Hematology/Oncology, Department of Internal Medicine, and associate professor of medicine, Mayo Clinic, discusses 2 agents that have advanced the treatment landscape for patients with thyroid cancer, including the multi-tyrosine kinase inhibitor (TKI) lenvatinib (Lenvima) and another TKI, sorafenib (Nexavar).

In the past, patients with thyroid cancer were primarily treated with chemotherapy, according to Tan. However, the progression-free survival (PFS) with chemotherapy was very short. Lenvatinib and sorafenib both have proven to prolong PFS. Lenvatinib could extend PFS by at least 1 year or longer, and sorafenib prolongs PFS by at least 6 months.

Winston Tan, MD, discusses 2 agents that have advanced the treatment landscape for patients with thyroid cancer, including the multi-tyrosine kinase inhibitor lenvatinib and another TKI, sorafenib.

Treatments Improve PFS in Thyroid Cancer

Diagnosis of a 69-Year-Old Woman With Follicular Lymphoma

Follicular Lymphoma: Prognostic Scoring and Treatment Decisions

Maintenance Therapy for Follicular Lymphoma

Follicular Lymphoma: Treating Early Progression

PI3K Inhibition for R/R Follicular Lymphoma

Treating R/R Follicular Lymphoma With PI3K Inhibitors

Novel Therapies for Patients With Follicular Lymphoma

Case:A 69-Year-Old Woman With Follicular Lymphoma

A 69-year-old woman complains of a 5-month history of fatigue, decreased appetite and a 10-bs. weight loss

PE: right axillary and bilateral cervical lymph nodes palpated ~ 3 cm; spleen palpable 4 cm below costal margin



Labs: ANC 1.6 x 109/L, WBC 11.8 x 109/L, 40% lymphocytes, Hb 8.9 g/dL, plt 98 x 109/L, LDH 308 U/L, B2M 3.7 µg/mL; HBV negative

Excisional biopsy of the lymph node on IHC showed CD 20+, CD 10+, BCL2+; follicular lymphoma grade 2

Bone marrow biopsy showed paratrabecular lymphoid aggregates, 45% involvement

PET/CT showed enlargement of right axillary lymph nodes (3.1 cm, 3.2 cm), diffusely enlarged nodes in the retroperitoneal and lumbar lymph nodes

She was treated with R-CHOP for 6 cycles with rituximab maintenance; achieved partial response

5 months later she complained of increasing fatigue

Repeat PET/CT revealed progression of disease

She was started on bendamustine + obinutuzumab for 6 cycles and continued maintenance obinutuzumab

Repeat lymph node biopsy remained grade 1-2 follicular lymphoma

9 months later she complained of chills and low-grade fever

She was started on idelalisib 150 mg PO BID

Ajay K. Gopal, MD, discusses the rationale for treating a 69-year-old woman with high-risk follicular lymphoma with a PI3-kinase inhibitor in the third-line setting.

A 69-Year-Old Woman With Follicular Lymphoma

A group of gynecologic oncologists spoke to the challenges they have seen in their clinics in the face of the coronavirus disease 2019 (COVID-19) pandemic.

Chad A. Hamilton, MD, of the Inova Health System, says that almost every facet of business has been impacted by COVID-19, although it depends a lot on the prevalence of COVID-19 in different areas of the country. At his center in Virginia, there are many changes the patient will see within their first 15 minutes of walking into the clinic, which includes the removal of chairs in the waiting room; limited number of companions they can bring, although most times these family members and caregivers are asked to wait in the car; and everyone is masked.

Thomas C. Krivak, MD, of the Allegheny Health Network in Pennsylvania, notes that his area, Pittsburgh, is a lower impact area than others, and his institution was ahead of the game as they had converted to telemedicine fairly early on during the pandemic. However, patients with gynecologic cancers have limitations in regard to what visits can be done virtually. An important part of their visits is the pelvic exam, which telemedicine can not accommodate.

There is a lot of fear in patients, but Krivak says he is more comfortable coming into work than going somewhere like the grocery store because of all the screening questions at the door and extra precautions being taken in the hospital setting. However, the clinic is seeing about 40% fewer patients than they used to, and he expects there will be a delay in diagnosis over the next few months for patients with gynecologic cancers.

Shannon N. Westin, MD, of The University of Texas MD Anderson Cancer Center, agrees that patients aren’t necessarily seeing their physicians or are possibly deferring visits for evaluation of symptoms of concern. At her center in Texas, they are beginning to see patients again with the normal precautions Hamilton mentioned, but the majority of visits are still telemedicine-based. However, she is beginning to see new patients and new consults in person when it’s possible or necessary.

<< View more resources and information in gynecologic cancers

A group of physicians in gynecologic oncology spoke to the challenges they have seen in their clinics in the face of the COVID-19 pandemic.

Experts Discuss How COVID-19 Has Impacted Gynecologic Oncology Practices

Charles L. Sawyers, MD, internist and hematologic oncologist; chair of the Human Oncology and Pathogenesis Program; and Marie-Josée and Henry R. Kravis Chair at Memorial Sloan Kettering Cancer Center, discusses the value of atezolizumab (Tecentriq), cobimetinib (Cotellic), and vemurafenib (Zelboraf) in the melanoma treatment landscape.

The phase 3 IMspire150 trial (NCT02908672) investigated this triplet regimen in patients with previously untreated patients with metastatic or unresectable locally advanced melanoma and a 

V600 mutation. The trial showed efficacy of this triplet regimen by meeting its primary end point of progression-free survival (PFS). Sawyers says that although it is great that it worked for these patients, the field has moved forward at a rapid pace.

Although the comparison in this trial was compelling at the time it was designed, it’s now troubling because the standard of care for these patients is ipilimumab (Yervoy) and PD-1/PD-L1 antibodies, which has shown impressive efficacy in early trials and in a 5-year follow-up, according to Sawyers. About 40% of patients have PFS at 5 years, which may be hard to surpass with the IMspire150 trial. Comparisons of these 2 types of regimens are moving forward in this setting.

Charles L. Sawyers, MD, discusses the value of atezolizumab, cobimetinib, and vemurafenib in the melanoma treatment landscape.

The Importance of IMspire150 Data Is Questioned in Melanoma Treatment Landscape

Evolution of Targeted Therapy in Advanced NSCLC

Targeted Therapy in NSCLC: Improvements in Molecular Testing

History of KRAS Testing in Advanced NSCLC

An Overview of KRAS Tumor Biology

Shared insight on recent advances in KRAS-mutant NSCLC, with a focus on new therapies on the horizon.

Targeting KRAS Mutations in Advanced NSCLC

Bradley J. Monk, MD, FACS, FACOG, co‐director of GOG Partners, Arizona Oncology (US Oncology Network); professor of Gynecologic Oncology at University of Arizona, Creighton University; and medical director of the US Oncology Research Gynecology Program, discusses the remaining challenges in conducting clinical trials for patients with cervical cancer.

Clinical trials evaluating treatments for patients with cervical remains difficult at this time, says Monk. These patients with cervical cancer often are younger than what is traditionally observed in gynecologic cancers. The average age of women with cervical cancer is late 40s to early 50s, so these women often still have children at home, compared with patients with ovarian cancer or endometrial cancer who are usually around 60 to 70 years old.

Cervical cancer also remains underdeveloped in many ways, Monk notes. The screening paradigm and the vaccination paradigm did not provide patients with cervical cancer an exceptional opportunity for treatment in clinical trials. Overall, Monk says that at its core, clinical research in cervical cancer remains complicated.

<< View more resources and information in cervical cancer

Bradley J. Monk, MD, FACS, FACOG, discusses the remaining challenges in conducting clinical trials for patients with cervical cancer.