This month’s cover story provides an evaluation of marijuana's impact on fertility and pregnancy.

Vol 66 No 10: October 2021

As technology takes a starring role in healthcare, patients are seeking user-friendly experiences from their healthcare provider.

 from healthcare communication platform Updox, a patient experience survey found that 51 percent of respondents say that user-friendly technology is important to a good patient experience. A further 53 percent say that they would most prefer to update or provide their patient information, such as health conditions and new prescriptions, digitally via online forms accessed securely by mobile phone, email, or patient portal. Another 55 percent say convenient communications as key to their having a good patient experience.

“It’s clear that COVID-19 has impacted and even accelerated the expectations and preferences of patients and the ways they prefer to engage with and receive care from their healthcare provider,” Zach Zettler, president of Updox, says in the release. “It is critical for practices to adjust to these needs to better connect with patients where they are – on their phones. When it comes to technology solutions that consumers believe are important for a healthcare provider to offer, it’s all digital.”

The pandemic has also changed patients’ expectations of healthcare. Some of what patients now expect include:

42 percent expect electronic forms or online paperwork options

41 percent expect direct access to their healthcare provider over the phone, video calls, text messaging, or emails

41 percent expect telehealth appointment options to be available

39 percent say they expect communications can be conducted virtually

37 percent expect virtual waiting room options

“Communication can truly be a huge barrier in getting healthcare services, which is why it’s so important for today’s providers to focus first on establishing relationships,” Sherie Garrison, RN, of Luke Project 52 Clinic, says in the release. “At my clinic, Updox really is the glue we use to build trust with our patients. Texting with them isn’t always medically related — it’s a way to show we care about them, and we’re connected to them.”

This article was originally posted on Medical Economics®. 

Articles

Patients are looking for user-friendly technology.

What matters for a good patient experience? 

A team of investigators led by Katarina Remaeus, PhD, Karolinska Institutet, Department of medicine Solna, Clinical Epidemiology Division, conducted a cohort study in order to evaluate the impact that antirheumatic treatment had on pregnancy outcomes in women with psoriatic arthritis (PsA).

Investigators found that the risk of adverse outcomes increased the most in pregnancies with antirheumatic treatment, especially those treated with biologic disease modifying antirheumatic drugs (bDMARDs), during pregnancy, compared with non-psoriatic arthritis.

Of the few previous studies that describe maternal and neonatal pregnancy outcomes in women with psoriatic arthritis, some indicated an increased risk of preterm birth and cesarean delivery.

Investigators conducted a nationwide Swedish register-based cohort study of births from July 2007-December 2017 to compare pregnancy outcomes, with a focus on presence and timing of antirheumatic treatment in pregnancies with exposure to psoriatic arthritis compared with pregnancies without exposure to PsA.

Exposure to psoriatic arthritis was defined by women with a diagnosis of psoriatic arthritis in the NPR according to International Classification of Diseases (ICD)-10 codes L405, M070-1, and M073. First and subsequent pregnancies of these women were identified by linkage to the medical birth registry (MBR).

Unexposed pregnancies or non-psoriatic arthritis pregnancies were identified from the NPR and by the medical birth registry, the first and subsequent singleton pregnancies to women without diagnosis of inflammatory joint disease sampled from a pre-existing linkage.

In total, 921 psoriatic arthritis pregnancies and 9210 non-psoriatic arthritis pregnancies were identified by investigators. There were 10 unexposed pregnancies sampled matched on year of birth, maternal age, and parity.

Investigators used the prescribed drug register (PDR) to gather information on dispensed prescriptions for antirheumatic treatment. Antirheumatic treatment was defined as oral corticosteroids, conventional (cs) or biological (b) disease modifying antirheumatic drugs (DMARDs).

Of the 921 psoriatic arthritis pregnancies, 495 were pregnancies without any prior treatment for PsA in the year before pregnancy up until delivery and 426 were pregnancies with presence of any antirheumatic treatment within the same time frame.

The pregnancies were then further stratified, all based on presence and timing of maternal antirheumatic treatment and compared to the matched 9210 non-psoriatic pregnancies.

Results demonstrated that pregnancy outcomes varied with timing, presence and type of antirheumatic treatment.

The risk of adverse outcomes were found to be most increased in pregnancies with antirheumatic treatment, especially biologic disease modifying antirheumatic drugs, during pregnancy, compared with non-psoriatic arthritis.

Overall, the risk of preterm birth was increased for the main analysis of the 921 psoriatic arthritis pregnancies (aOR of 1.69, 95%CI 1.27-2.24).

The increased risks for spontaneous onset and medically indicated preterm birth were statistically significant, as well as for moderately, but not for very preterm birth. Elective (aOR 1.77, 95%CI 1.43-2.20) and emergency (aOR 1.42 95%CI 1.10-1.84) cesarean delivery showed an increased risk also.

The results displayed no differences in risk of pre-eclampsia, gestational diabetes or hypertension, small for gestational age, or large for gestational age in psoriatic arthritis pregnancies compared to non-psoriatic arthritis pregnancies.

Investigators recommended that all women with psoriatic arthritis should be counseled about pregnancy outcomes and receive individualized monitoring during pregnancy, regardless of antirheumatic treatment.

Pregnancy outcomes in women with psoriatic arthritis with respect to presence and timing of antirheumatic treatment

This article was initially published by our sister publication HCP Live.

The study examines the impact of antirheumatic treatment on pregnancy outcomes in women with psoriatic arthritis.

Pregnancy outcomes vary in women with psoriatic arthritis

It’s no secret that girls are entering puberty earlier and earlier, but a new study suggests that it’s happening as rapidly as 3 months earlier with each decade of women.1

How the onset of puberty for women is gauged can be debated, with many studies focusing on a woman’s recall of her age at her first period (menarche) as a benchmark. New literature, however, turns the focus to breast development as the most reliable tool for measuring progress through puberty in girls.

Katherine Kutney, MD, a pediatric endocrinologist at Rainbow Babies and Children’s Hospital in Cleveland, Ohio, said that, like in boys, physical indicators are a better way to diagnose the onset of puberty in the clinical setting.

For both boys and girls, the puberty process is triggered by the activation of the hypothalamic-pituitary-gonadal (HPG) axis. For boys, this causes testicular growth, which is the first clinical sign that a male has entered central puberty. For girls, although first menstruation might traditionally have been considered to be a sign that puberty has begun, it actually begins with thelarche, or breast development.

Tanner staging, also known as the Sexual Maturity Rating (SMR) scale, is the standard system for measuring progress through puberty, Kutney said. For boys, this scale assigns stages to signify progress through puberty based on pubic hair and genitalia development. For girls, the scale uses measurements of breast tissue and public hair development.

Pubic hair development, a process called adrenarche, can occur at the same time as thelarche, but it doesn’t always. This process, which is triggered with the release of female sex hormones, spurs the growth of pubic and axillary hair, the development of adult body odors, and acne.

Stage 3: Thicker, darker (terminal) hair begins to develop

Stage 4: Terminal hair covers the entire triangle of the pubic region

Stage 5: Terminal hair covers the entire triangle of the pubic region and extends past the inguinal crease to the thigh

Stage 1: No palpable glandular breast tissue

Stage 2: A breast bud can be felt under the areola

Stage 3: Breast tissue can be felt outside the areola, but there is no further development of the areola itself

Stage 4: The areola develops above the contour of the breast

Stage 5: The areola recedes back into the contour of the rest of the breast and takes on a darker pigmentation, papillae development, and protrusion of the nipple

Earlier onset of puberty in girls has been noted for some time, but the 2020 study suggests that it has progressed to such a point that guidelines may need to be adjusted to redefine precocious, or “early,” puberty designations. Kutney said the average onset of puberty for girls is around age 10 years, but it can occur in as young as 8 years of age for girls from African American and Hispanic ethnicities. The upper age limit for puberty onset in girls is age 12 years, she added.

1. Eckert-Lind C, Busch AS, Petersen JH, et al. Worldwide secular trends in age at pubertal onset assessed by breast development among girls: a systematic review and meta-analysis. 

 2020;174(4):e195881. doi:10.1001/jamapediatrics.2019.5881

2. Emmanuel M, Bokor BR. Tanner stages. StatPearls Publishing. 2021.

This article was originally published on Contemporary Pediatrics®. 

Age of first menarche has long been seen as a girl's start to puberty, but breast development may be a better fit.

Puberty happening 3 months earlier in each decade of women

Pink October video shines light on women’s health — and their right to know prices

Every October, the pink ribbons and flamingoes come out to raise breast cancer awareness. However, Pink October should go beyond breast cancer awareness to shine the light on women’s health overall, and, as important, the huge responsibility women bear as chief decision-makers for their families’ health care.

Agenus Withdraws BLA for Balstilimab in Metastatic Cervical Cancer

The immuno-oncology company Agenus has made the decision to withdraw its biologic license application for the use of the PD-1 inhibitor balstilimab in patients with recurrent or metastatic cervical cancer who experienced disease progression on, or after, chemotherapy.

Poll: Have you attended an in-person conference recently? 

Here's a preview of what to expect this week from Contemporary OB/GYN®. 

This week on Contemporary OB/GYN®: Oct. 25 to Oct. 29

The immuno-oncology company Agenus has made the decision to withdraw its biologic license application (BLA) for the use of the PD-1 inhibitor balstilimab in patients with recurrent or metastatic cervical cancer who experienced disease progression on, or after, chemotherapy.1

 (Keytruda) on October 13, 2021, for use as a single agent in patients with recurrent or metastatic cervical cancer with disease progression on, or after, chemotherapy and whose tumors have a PD-L1 combined positive score of 1 or higher, as determined by a FDA-approved test.2 In light of this decision, the FDA no longer considered it appropriate to review the balstilimab application for accelerated approval and recommended that Agenus withdraw.

The application was supported by data from a 

 (NCT03894215), which showed that balstilimab elicited a confirmed objective response rate (ORR) of 15% (95% CI, 10.0%-21.8%; n = 21/140); this included a complete response (CR) rate of 3.6%, a partial response (PR) rate of 11.4%, and a stable disease rate of 36.4%. Forty percent of patients had progressive disease.3

Moreover, in patients with PD-L1 positivity (n = 85), balstilimab induced an ORR of 20.0%; in those with PD-L1 negativity (n = 38), the ORR with the agent was 7.9%.

“While the commercial market for balstilimab monotherapy in second-line cervical cancer is always anticipated to be small, Agenus’ priority remains developing balstilimab as a necessary component of highly effective and affordable combination therapies, both with its own portfolio and with partners, including in combination with Agenus’ next-generation CTLA-4, AGEN1181,” Garo Armen, chief executive officer and chairman of Agenus, stated in a press release.

The open-label, single-arm, global phase 2 trial enrolled patients with a pathologically confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, with metastatic, persistent, or recurrent disease.

To be eligible for enrollment, patients needed to be at least 18 years of age, have an ECOG performance status of 0 or 1, and acceptable hematologic, renal, and hepatic function. Patients also needed to have at least one measurable lesion per RECIST v1.1 criteria, disease that had relapsed following a first-line, platinum-based regimen. Notably, patients were enrolled irrespective of PD-L1 expression status.

If patients previously received immune checkpoint inhibitor therapy, known hypersensitivity to humanized monoclonal antibodies, or if they received more than 1 systemic regimen for advanced cervical cancer, they were excluded.

Study participants were given intravenous balstilimab at a dose of 3 mg/kg once every 2 weeks, given as a 60-minute infusion. This dose was determined to be the recommended phase 2 dose based on findings from the run-in phase 1 dose-escalation portion of the trial. Treatment continued for up to 24 months or until progressive disease, unacceptable toxicity, or investigator or patient decision.

The primary end point of the trial was ORR per independent end point review committee in accordance with RECIST v 1.1 criteria. Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival, and overall survival. An exploratory end point was focused on the association of PD-L1 expression and clinical response.

The median age of the 161 patients enrolled was 53 years (range, 25-81) and 52.2% had an ECOG performance status of 1. The distribution of histology was squamous cell carcinoma (62.7%), adenocarcinoma (32.3%), and adenosquamous carcinoma (4.3%). All patients were previously exposed to platinum treatment and 29.2% received bevacizumab (Avastin) as part of a prior regimen.

Moreover, 61.5% of patients had tumors with PD-L1 positivity and 26.7% had PD-L1 negativity. The rest of the cases, or 11.8%, were not evaluable for PD-L1 expression or did not have that information available. Among those with PD-L1–positive tumors, 23.2% previously received bevacizumab.

The median duration of follow-up was 14.6 months (range, 9.9-38.8). The median DOR with balstilimab was 15.4 months (95% CI, 5.7–not reached). The 6-month response rate was 12%; at 9 months and 12 months, these rates were 8% and 6%, respectively. The DCR with balstilimab was 49.3% (95% CI, 41.1%-57.5%).

Responses were observed across all histologic subtypes, including tumor responses that were reported in 12.5% if those with cervical adenocarcinomas. Moreover, 33.6% of patients previously received bevacizumab and 5 of these patients responded to treatment with balstilimab; this included 1 CR and 4 PRs and translated to an ORR of 10.6%.

Regarding safety, the most common any-grade treatment-related toxicities included asthenia (23%), diarrhea (12.4%), pruritis (11.8%), and fatigue (10.6%). The majority of the effects were grade 1 or 2 in severity. The incidence of grade 3 or higher treatment-related adverse effects (TRAEs) was 11.8%, with 3.1% of patients experiencing immune-mediated enterocolitis.

Moreover, 7.5% of patients experienced at least 1 serious TRAE, the most common of which was immune-mediated enterocolitis. Twenty-three patients experienced a TRAE that resulted in dose interruption and 7 patients had a TRAE that led to discontinuation. One death was determined to be potentially related to treatment; the patient died of an unknown cause.

Agenus announced plans to discontinue the ongoing confirmatory phase 3 BRAVA trial (NCT04943627), which is examining balstilimab monotherapy or investigator’s choice of chemotherapy, which could include gemcitabine, irinotecan, pemetrexed, vinorelbine, or topotecan, in patients with recurrent, persistent, or metastatic cervical cancer who have progressed following platinum-based chemotherapy.

However, due to the clinical benefit reported with the immunotherapy, the company announced plans to launch expanded access programs to provide patients and providers with access to the agent in several countries, including the United States, following regulatory processes.

“Balstilimab has demonstrated meaningful clinical activity and an excellent safety profile in second-line cervical cancer, including in PD-L1–negative patients, who are ineligible to receive standard-of-care anti–PD-1 therapy, which makes the decision to withdraw so difficult for us,” Steven O’Day, MD, chief medical officer of Agenus, stated in the press release. “Balstilimab remains a critical component of our combination regimens, including with our next-generation CTLA-4 agent, AGEN1181. Concomitant with the presentation of new data at SITC next month, we continue to accelerate development of AGEN1181 in combination with balstilimab in trials designed to rapidly support full or accelerated approval in multiple tumor types.”

Agenus provides update on balstilimab development. News release. Agenus. October 22, 2021. Accessed October 22, 2021. 

FDA approves pembrolizumab combination for the first-line treatment of cervical cancer. News release. FDA. October 13, 2021. Accessed October 22, 2021. 

O’Malley DM, Oaknin A, Monk BJ, et al. Phase II study of the study and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer. 

. Published online August 24, 2021. doi:10.1016/j.ygyno.2021.08.018

This article was originally published on OncLive®. 

Consideration of policy solutions to address regulatory barriers of care is also proposed by a working group of 13 experts convened by the Society for Women's Health Research. In addition, providers need to factor in the diverse needs of individuals experiencing 

 in the development of their personalized care.

The experts encompass patient advocates and policy leaders, as well as clinical specialists and researchers in gynecology, reproductive endocrinology, psychiatry, and epidemiology.

“Menopause is often stigmatized and framed as if it were a disease, as opposed to a natural part of a woman's life cycle,” wrote the authors. “A holistic patient care model that emphasizes earlier and more robust education about the menopause transition for patients and providers would aid in the normalization of this life transition and improve quality of life for patients.”

The menopause transition can span up to 20 years. Some postmenopausal women are also at increased risk for serious health conditions like cardiovascular disease, osteoporosis, and diabetes. With increases in life expectancy, a woman's postmenopause phase may represent up to 40% of her life.

But without adequate preparation and/or symptoms not well-managed, the menopause transition might exacerbate conditions that impair quality of life and life expectancy; therefore, the authors advise providers to prepare women as young as age 35 for better overall health during the menopause transition and postmenopause.

A personalized approach to care is recommended because menopausal symptoms and experiences vary widely, based on age of onset, overall patient health and the patient’s specific type of menopause.

Providers should consider which symptoms an individual is experiencing that impede quality of life, along with available interventions: medical, lifestyle and/or behavioral.

Structured physical activity and yoga are 2 lifestyle interventions that can improve perimenopausal and postmenopausal quality of life. However, while aerobic exercise is an effective approach to managing mood, its usefulness has not been proven for managing vasomotor symptoms (VMS). Meanwhile, cognitive behavioral therapy and mindfulness-based therapies are often efficacious in managing the bother and interference of VMS.

Furthermore, provider training might help curtail the use of custom-compounded hormone products that are not regulated by the FDA and that lack evidence of safety or efficacy.

Enhanced medical curriculum on menopause is also proposed, not only for ob-gyns, but for the spectrum of health care providers for women in midlife, including primary care and mental health professionals.

“Without menopause-specific education, providers can easily misunderstand or dismiss menopause symptoms related to irregular menstrual cycles or heavy bleeding, mood, vaginal symptoms, and disordered sleep,” wrote the authors.

Collecting data from diverse populations on the intersections of menopause and race, gender, culture, and socioeconomic status will better inform key stakeholders on developing personalized care, according to the authors.

Also needed is intentional accommodation of menopause in the workplace, such as flexible leave policies, which has gained momentum in countries like Australia and the United Kingdom.

Aninye IO, Laitner MH, Chinnappan S.Menopause preparedness: perspectives for patient, provider, and policymaker consideration. 

A more standardized approach to menopause preparedness, including educating both patients and providers, is needed to improve care and quality of life for individuals during and after menopause, according to a study in the journal Menopause. 

Menopause preparedness for patient, provider, and policymaker

Poll

Whether you practice in Texas or not, the strict abortion ban may be an influencing factor for many abortion providers. 

Poll: Has the Texas abortion ban impacted the way you treat patients? 

Minority and medically underserved breast cancer survivors experienced significant health benefits after participating in a community-based physical activity program, according to recently published study results.

The data — which were published in the journal 

 — demonstrated that participation in a 12-week program that was tailored to individuals in a community setting improved several mental and physical health outcomes among a diverse group of breast cancer survivors.

The program, known as Active Living After Cancer, consists of 12 weekly group sessions which provides survivors with training in cognitive and behavioral skills for behavior change, brief physical activity, and cancer survivorship-related content.

This particular program was adapted from an evidence-based plan and tailored to individuals who are of minority race or more prone to being medically underserved.

Karen Basen-Engquist, a co-author on this study and a director of the Center for Energy Balance in Cancer Prevention and Survivorship at The University of Texas MD Anderson Cancer Center in Houston, explained in an interview with CURE® that not all cancer survivors have the adequate means to access fitness resources, such as a gym or personal trainer. As a result, this program was developed and offered to participants for free. The program was also offered in Spanish as there aren’t many programs that have that benefit, she said.

This study included 127 breast cancer survivors. Participants completed assessments of their physical activity, quality of life and physical functioning (six-minute walk distance and 30-second sit-to-stand test) at the start of the trial and at a 12-week follow-up.

Physical activity significantly improved from 17.8 minutes per week at the start of the trial to 344.6 minutes per week at follow up. Basen-Engquist explained that this was an important improvement not just for the management of symptom, but also because there is additional research that those who are physically active are less likely to die of cancer.

Debbie Mendoza, who was diagnosed with metastatic breast cancer in February 2019, completed her treatment in March 2020 and was left without any energy. She participated in the Active Living After Cancer program and noted that she benefitted from it. Before the program started, she said she could only walk up her street and back — now she is walking a mile and a half or 30 minutes with her dog every day.

“For me, I got lots of confidence, I feel much stronger now,” Mendoza said in an interview.

The study results also demonstrated that distance in the six-minute walk and the sit-to-stand test improved significantly from the start of the trial to follow up.

Of note, cancer survivors often go through an accelerated aging process, Basen-Engquist explained, meaning they tend to physically and mentally age more after a cancer diagnosis. The improvements in six-minute walk and sit-to-stand test are important, according to Basen-Engquist, because that activity can reverse the aging process and allow survivors to return to performing daily tasks.

“If we can help improve people’s performance on tests like these, this indicates that maybe we’re starting to arrest that accelerated aging and reverse it,” she said.

There were also statistically significant improvements in physical and 

 from the start of the trial to follow up. Mendoza said she physically feels “so much better now.” And mentally, her quality of life improved as well.

Mendoza was just finishing her treatment when the COVID-19 pandemic was beginning. Because she was immune compromised, she could not see many people. However, she noted that the program gave her a sense of community. She said it was good to talk to people online who were going through the same journey.

“We were really happy to see that when it’s done in kind of a real-world setting, that we still see that the program is effective,” Basen-Engquist added.

Basen-Engquist also highlighted that physical activity may be beneficial for all breast cancer survivors, regardless of race, because it has been shown to reduce the risk of a chronic disease associated with a cancer diagnosis. She explained that breast cancer survivors, diagnosed with stage 1 to 3 disease, are more likely to 

, rather than their cancer, and physical activity may help reduce this risk. Additionally, those survivors who are physically active might be less likely to have a cancer recurrence, she said.

“In addition to potentially affecting the cancer-related outcomes, we’re also having a positive influence on other chronic diseases,” Basen-Engquist noted.

Recommendations for Breast Cancer Survivors

After the 12-week program ended, 83% of participants implemented two or more behavioral changes they had learned during the program into their life. Almost all the participants (98%) were satisfied with the program and would recommend it to another cancer survivor. Moreover, most participants reported that the program helped them become more physically active (97%) and feel better physically (92%) and emotionally (83%).

Mendoza is one of the many participants who implemented these changes after the study ended, and physical activity is now a part of her daily routine. Before the program started, she didn’t believe that exercising would give her more energy, because she didn’t have energy to exercise in the first place. When the study had finished, she said she was doing a form of physical activity about four times a week, which has now increased to every day.

Basen-Engquist recommended that breast cancer survivors who want to become more active to talk to their oncologist and see what resources are available to them. A great place to start, she noted, is to walk, and then incorporate longer walks or brisk walks for 10 minutes at a moderate pace.

This article was originally published on Cure®. 

Medically underserved and minority breast cancer survivors experienced improved outcomes and quality of life after participating in community-based physical activity programs, according to recent study results.

Community-based activity programs benefit underserved breast cancer survivors

American College of Gastroenterolgy 2021 conference

, Rawan Aljaras, MD, Indiana University School of Medicine, discussed the various ways in which diet can influence a patient’s 

Aljaras explained how important it is to continuously monitor trends in diet because of how closely related diet is to the gastrointestinal system. Certain diets have been proven to affect bowel movements and multiple gastrointestinal disorders.

When asked about an optimal diet for irritable bowel syndrome patients, Aljaras stressed the importance of fiber.

She reflected on how making dietary lifestyle changes can be a difficult process for a patient. Working with the patient to take baby steps and view the goal as a moving target is her focus.

“I feel like it’s always very easy for us as physicians to talk to patients about committing to lifestyle changes,” Aljaras said. “It's never easy in real life.”

As for the effect that the pandemic has had on patients’ diets, Aljaras said the impact was negative for everyone. She emphasized the amount of stress that came with the pandemic.

Many people were trying to keep up with life as usual even through the stress of quarantine. The impact of this could potentially be seen by doctors as a result of the poor dietary habits developed throughout this time and the effect they could have on the gastrointestinal system.

Watch the full interview originally published on HCP Live®. 

Dr. Aljaras talks about the importance of focusing on diet when examining irritable bowel syndrome.

The impact of diet on IBS

The FDA has granted a fast track designation to the interleukin-2 (IL-2) variant immunotherapy nemvaleukin alfa (nemvaleukin) in combination with pembrolizumab (Keytruda) for the treatment of patients with platinum-resistant ovarian cancer.

The investigational engineered fusion protein is composed of modified IL-2 and the high affinity IL-2 alpha receptor chain, which preferentially expands tumor-killing immune cells and avoids the activation of immunosuppression cells through selective binding to the intermediate-affinity IL-2 receptor complex. The selectivity of the agent is hypothesized to leverage the antitumor effects of existing IL-2 therapy and diminish select limitations.

Nemvaleukin plus pembrolizumab will be compared with investigator’s choice of chemotherapy in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, as part of the global, open-label, phase 3 ARTISTRY-7 trial (NCT05092360), which was initiated on October 26, 2021.

Additional nemvaleukin and pembrolizumab monotherapy arms will also be evaluated.

“The fast track designation in platinum-resistant ovarian cancer highlights the potential clinical utility of nemvaleukin in combination with pembrolizumab in this difficult-to-treat disease for which there is no approved immunotherapy and there remains significant need for new treatment options,” Craig Hopkinson, MD, chief medical officer and executive vice president of Research & Development at Alkermes plc, stated in a press release. “We are excited to initiate…[the] ARTISTRY-7 phase 3 trial in platinum-resistant ovarian cancer, as we advance nemvaleukin toward potential registration and seek to help patients living with this disease.”

To be eligible for enrollment to ARTISTRY-7, patients need to be at least 18 years of age, have platinum-resistant or -refractory disease, have received at least 1 previous line of systemic therapy in the platinum-sensitive setting, have at least 1 measurable lesion per RECIST v1.1 criteria, and be willing to undergo a pretreatment tumor biopsy.

If patients had primary platinum-refractory disease or primary platinum resistance, a histologically confirmed diagnosis of epithelial ovarian carcinoma with mucinous or carcinosarcoma subtype, or a nonepithelial tumor, they will be excluded. Other exclusion criteria include having previously received IL-2–based or IL-15–based cytokine therapy and prior exposure to any anti–PD-1/PD-L1 therapy.

Participants will be centrally allocated in a randomized 3:1:1:3 fashion to receive either nemvaleukin and pembrolizumab, pembrolizumab monotherapy, nemvaleukin monotherapy, or investigator’s choice of chemotherapy, which could include 1 of the following: pegylated liposomal doxorubicin (PLD), paclitaxel, topotecan, or gemcitabine.

Nemvaleukin will be given at a daily dose of 6 µg/kg on days 1 through 5 of 21-day treatment cycles. Pembrolizumab will be administered at a dose of 200 mg on day 1 of each 21-day cycle. PLD will be given at 40 mg/m2 on day 1 of 28-day cycles; paclitaxel will be given at 80 mg/m2 on days 1, 8, 15, and 22 of 28-day cycles; topotecan will be given at 4 mg/m2 on days 1, 8, and 15 of 28-day cycles; and gemcitabine will be given at 1000 mg/m2 on days 1 and 8 if 21-day cycles.

The primary end point of the trial is investigator-assessed progression-free survival based on RECIST v1.1 criteria. Additional end points include objective response rate, overall survival, disease control rate, duration of response, time to response, cancer antigen-125 response, pharmacokinetics, pharmacodynamics, and safety.

Investigators plan to enroll approximately 376 patients to the trial.

“The initiation of our phase 3 study of nemvaleukin in platinum-resistant ovarian cancer is an important milestone for the nemvaleukin clinical development program and reflects our commitment to focusing on the high unmet need of patients living with difficult-to-treat cancers such as platinum-resistant ovarian cancer,” Hopkinson stated in a press release. “ARTISTRY-7 is designed to build upon the durable and deepening responses observed in heavily pretreated patients with platinum-resistant ovarian cancer in the ongoing ARTISTRY-1 trial [NCT02799095]. We look forward to sharing updates from ARTISTRY-7 as the study progresses and as we advance toward potential registration.”

FDA granted a fast track designation to nemvaleukin for the treatment of patients with mucosal melanoma

 In the phase 2 ARTISTRY-6 trial (NCT04830124), investigators are evaluating the antitumor activity, safety, and tolerability of nemvaleukin in this patient population. The study also includes a cohort of patient with advanced cutaneous melanoma who will receive subcutaneous nemvaleukin with the intent to establish single agent proof-of-concept with the latter dosing.

This article was initially published by our sister publication Onc Live.

Alkermes receives FDA fast track designation for nemvaleukin alfa in combination with pembrolizumab for the treatment of platinum-resistant ovarian cancer. News release. Alkermes plc. October 25, 2021. Accessed October 26, 2021. 

Alkermes initiates ARTISTRY-7 phase 3 trial of nemvaleukin alfa in patients with platinum-resistant ovarian cancer. News release. Alkermes plc. October 26, 2021. Accessed October 26, 2021. 

Phase 3 study of nemvaleukin alfa in combination with pembrolizumab (ARTISTRY-7). ClinicalTrials.gov. Updated October 25, 2021. Accessed October 26, 2021. 

https://www.clinicaltrials.gov/ct2/show/NCT05092360

Alkermes receives FDA fast track designation for nemvaleukin alfa for the treatment of mucosal melanoma. News release. Alkermes plc. August 2, 2021. Accessed October 26, 2021. 

Alkermes initiates ARTISTRY-6 trial of nemvaleukin alfa monotherapy in patients with melanoma. News release. Alkermes plc. April 27, 2021. Accessed October 26, 2021. 

The FDA has granted a fast track designation to the interleukin-2 variant immunotherapy nemvaleukin alfa for use in combination with pembrolizumab in the treatment of patients with platinum-resistant ovarian cancer.