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If 2020 was dominated by the news of how COVID-19 spread across the globe, then 2021 has so far been focused on ending the pandemic through vaccine distribution.

A Timeline of COVID-19 Vaccine Developments in 2021

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As expected, on Monday, the FDA expanded the emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12 through 15.

The EUA was first issued in December 2020 for individuals 16 years and older.

The safety data to support the decision come from an ongoing, randomized, placebo-controlled clinical trial of 2260 adolescents. Of these, 1131 received the vaccine and 1129 received a placebo. More than half of the participants were followed for safety for at least 2 months following the second dose. The trial is based in the United States.

The most commonly reported adverse effects (AEs), which lasted about 1 to 3 days, were pain at the injection site, tiredness, headache, chills, muscle pain, fever, and joint pain.

As with adult recipients, AEs were more common and more pronounced after the second dose, which is given 3 weeks after the first.

“The FDA’s expansion of the emergency use authorization for the Pfizer-BioNTech COVID-19 vaccine to include adolescents 12 through 15 years of age is a significant step in the fight against the COVID-19 pandemic,” said Acting FDA Commissioner Janet Woodcock, MD, in a statement. “Today’s action allows for a younger population to be protected from COVID-19, bringing us closer to returning to a sense of normalcy and to ending the pandemic. Parents and guardians can rest assured that the agency undertook a rigorous and thorough review of all available data, as we have with all of our COVID-19 vaccine emergency use authorizations.”

From March 1, 2020, through April 30, 2021, approximately 1.5 million COVID-19 cases in individuals 11 to 17 years of age have been reported to the CDC. Compared with adults, children and teens generally have milder illness, but rare complications can develop.

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The FDA said vaccinating adolescents is another step in getting the country back to prepandemic life.

FDA Widens Pfizer-BioNTech COVID-19 Vaccine Indication to Include Adolescents

Note: This timeline will update throughout the year as new developments take place

March 11 represents the one-year anniversary since the World Health Organization declared COVID-19 a global pandemic, and shortly after, former President Donald Trump had declared a national emergency, with states beginning to issue stay-at-home orders, mask mandates, and capacity limits at businesses like restaurants and bars. For a full look at how the pandemic evolved throughout 2020, 

If 2020 was dominated by the news of how COVID-19 spread across the globe, putting normal life on hold for most people and overwhelming health care providers, then 2021 has so far been focused on ending the pandemic through vaccine distribution.

With research into hundreds of vaccine candidates, there are now 3 vaccines approved by the FDA. As of March 10, 

 that more than 93.6 million vaccine doses had been administered. Alaska, New Mexico, North Dakota, South Dakota, and Connecticut have administered the most doses per 100,000 of the total population. And with close to 10% of the US population fully vaccinated, updated guidance is starting to roll out.

Here is a look at how vaccine development, approval, and rollout has progressed so far in 2021.

Operation Warp Speed Initiates Talks With Moderna on Half-Dose Vaccines

Operation Warp Speed official Moncef Slaoui, MD, begins discussions with Moderna and the FDA regarding the possibility of 

 so as to double the number of people vaccinated against COVID-19. The announcement comes after data show that two 50-mcg doses of Moderna’s vaccine in individuals aged 18 to 55 years resulted in identical immune responses compared with the standard two 100-mcg doses.

UK Begins Distributing AstraZeneca/Oxford Vaccine

The United Kingdom begins to inoculate its population with the COVID-19 vaccine manufactured by 

, which can be stored at refrigerator temperatures between 2° and 8° Celsius, potentially enabling easier distribution. As a result of a highly transmissible variant of COVID-19 spreading throughout the United Kingdom, Prime Minister Boris Johnson hints at upcoming tighter restrictions.

FDA Advises Against Altering Vaccine Schedules

FDA issues a statement cautioning health care workers against making 

 to authorized dosing schedules for approved COVID-19 vaccines. The agency notes that potential changes would be premature and there is not enough evidence of their efficacy compared with approved 2-dose vaccine schedules.

Moderna to Produce 600 Million Vaccine Doses

 it will increase production from 500 million doses to 600 million doses for 2021 and plans to allocate resources to produce 1 billion doses in total this year. At this point, the company has supplied the US government with 18 million doses and projects to make nearly 100 million doses available to Americans by the end of the first quarter of 2021.

HHS to Provide $22 Billion to Fund Testing, Vaccine Distribution

HHS announces that the CDC plans to provide more than 

 in funding for states and territories to support the nation’s COVID-19 response, as a result of the Coronavirus Response and Relief Supplemental Appropriations Act. More than $3 billion of the sum will be made available through the CDC Immunization and Vaccines for Children cooperative agreement.

CDC: COVID-19 Vaccine Benefits Outweigh Allergic Reaction Risk

 to either the Pfizer/BioNTech or Moderna vaccine among nearly 2 million vaccinated Americans prompt the CDC to announce the incidences should not dissuade individuals from getting vaccinated. Of those who reported incidents, 20 fully recovered while most had a history of such reactions. The statement comes as the CDC anticipates the imminent spread of a highly contagious coronavirus variant, first reported in the United Kingdom, throughout the United States.

Study Shows Patients With Heart Failure Should Be Prioritized for Vaccines

Results of an investigation published in 

 find the risk of death from COVID-19 is reportedly twice as high in patients with acute 

The single-center study indicates these patients should be extra cautious to avoid contracting COVID-19 and ought to be considered a high-priority population as vaccine distribution begins.

American Hospital Association Pushes for Faster Vaccine Rollout

) sends a letter to HHS Secretary Alex Azar stressing that there should have been a universal COVID-19 vaccine rollout. The letter highlights 64 disparate plans being implemented, lack of standardized tasks needed to accomplish delivery, and a failure to provide progress reports compared with plan goals. According to the AHA, to achieve herd immunity 1.8 million individuals need to be vaccinated every day from January 15 through May 31.

Health officials begin to enlist regional and supermarket pharmacies ahead of schedule to address delays in vaccine rollouts, 

. Federal and state officials ask Rite Aid Corp., Kroger Co., Stop & Shop Supermarket LLC, and other retailers to administer vaccines to frontline workers and eligible vulnerable populations weeks before previously planned to troubleshoot protocols.

Biden Plans to Rapidly Release Most COVID-19 Doses

Then–President-Elect Joe Biden announces he will quickly release most available vaccine doses to inoculate more people, reversing Trump’s previous policies, according to the 

. Biden’s plan does not involve cutting 2-dose vaccines in half but accelerating shipments of first doses instead of holding second doses in reserve.

States and local health departments struggle to implement mass vaccination programs while facing a surge in COVID-19 cases and record-breaking hospitalizations, 

 reports. Staff shortages and shrinking budgets complicate efforts to receive, store, distribute, track, and administer vaccines, as well as monitor individuals for adverse events.

Biden’s goal remains 100 million vaccinations in 100 days, and he pledges to release all available doses, 

 Trump’s decision to hold back doses to ensure that second shots were available for those who had already received their first Pfizer/BioNTech or Moderna dose—at this point, the only approved COVID-19 vaccines. Rollout has been chaotic, as the CDC relegated responsibility to states to determine vaccination priority and extra doses built up in freezers or were trashed due to regulation confusion.

CDC, HHS Update Vaccine Allocation Guidance

 that forthcoming COVID-19 vaccine supplies will be based on to-this-point administration rates and each state’s total population of residents who are 65 years and older—but states have only 2 weeks to prepare. Vaccine rollout continues to be bumpy, and this update aims to address some of the issues hindering access to higher-risk individuals—health care and frontline workers, and those with comorbidities—with states possibly receiving fewer doses from lack of data reporting. All available vaccine doses are released, and distribution expands to pharmacies and community health centers.

Elderly Los Angeles County Residents Report Confusion, Delays

Conflicting messages from California Governor Gavin Newsom and local health officials lead to floods of phone calls and 

 inundated with appointment requests. While the governor said that Los Angeles County residents 65 and older were eligible to receive a COVID-19 vaccine, health officials reiterated that the group still has to wait. At this point, the city is in phase 1A of rollout (health care workers, skilled nursing and long-term care facility residents), and phase 1B eligibility (which includes people over age 65) is not slated to open until early February.

Limited pharmacy access, or living in a “pharmacy desert,” is predicted to affect access to available vaccines, with 

—the national average is just 1.83 pharmacies per 10,000 people—translating to more competition for fewer appointments and rural and urban areas alike being affected. At the time of this report, the authors predict that 423 counties had capacity to vaccinate only up to 10% of their combined populations and 177 had zero capacity because they didn’t have any pharmacies. Officials continue to sound the call for more mass vaccination sites and supportive infrastructure.

Ethnic and racial minorities continue to be disproportionately affected by the pandemic, with 

 showing Black Americans being vaccinated at rates 2 to 3 times below White Americans. COVID-19–related mortality, meanwhile, remains 3 times greater in Black, Hispanic, and Native American populations. Top reasons for these disparities, including among health care workers, are lack of access (ie, to technology and vaccines) and mistrust of the vaccine.

California COVID-19 Variant May Be Vaccine Resistant

Following genetic sequencing, researchers report that current vaccines may not be strong enough against 

, first identified in Denmark in March 2020 before surfacing in California in May. Prevalence of this variant is growing, with 1 comparison showing a jump from 3.8% of samples tested in late November to early December 2020 to 25.2% of samples tested in late December 2020 to early January 2021.

Pfizer, Moderna, AstraZeneca to Test Vaccines in Adolescents

With current vaccines still prioritized for older Americans and those with underlying heath conditions, as well as health care workers, 

 reveal their testing plans for younger Americans. Moderna is testing doses among 12- to 18-year-olds, Pfizer is said to have recruited 12- to 15-year-olds, and AstraZeneca and Oxford University report wanting to compare outcomes among 6- to 11-year-olds and 12- to 18-year-olds.

Incoming CDC Director Walensky to Prioritize Vaccine Rollout

Rochelle Walensky, MD, MPH, the soon-to-be 19th director of the CDC, 

 science-based communication in an effort to address vaccine hesitancy and antivaccination sentiment. Vaccine rollout continues to vary widely among states, and Walensky pledges to increase both vaccination sites and those administering doses to overcome these disparities, especially in harder-to-reach areas.

 in Novovax’s COVID-19 vaccine trial to see if they were administered a placebo and are eligible to receive the already-approved Pfizer/BioNTech or Moderna vaccine. Novovax’s phase 3 trial, which had a goal of 30,000 participants, has already been delayed by manufacturing lags despite a $1.6 billion infusion from Operation Warp Speed in July 2020. Accelerated expanded eligibility is also hindering recruitment of new trial enrollees.

California Reports Allergic Reactions to Moderna Vaccine

After vaccinations were paused on January 19 at a San Diego vaccination center due to 

 possibly related to lot 041L20A of Moderna’s COVID-19 vaccine, they are allowed to resume by the California Department of Public Health. The move follows discussions among allergy and immunology specialists, the CDC, the FDA, Moderna, and the County of San Diego Department of Public Health. This batch contained more than 1 million doses that were distributed to almost 1700 vaccination sites in 37 states, and California received 330,000-plus of these doses for 287 providers.

Pfizer Vaccine Effective Against United Kingdom’s B117 Variant

 from Pfizer and BioNTech indicates that the companies’ COVID-19 vaccine works just as well against a highly transmissible coronavirus variant, B.1.1.7, first discovered in the United Kingdom. Effectiveness against COVID-19 variants originating from South Africa and Brazil continue to be investigated, with experts noting that updated immunizations may be explored if the virus picks up enough significant mutations impacting the vaccines’ efficacy.

Amazon Offers to Help Distribute Vaccines

To assist Biden’s goal of vaccinating 100 million Americans against COVID-19 in his first 100 days in office, Amazon sent a letter to the president offering to help by leveraging the company’s operations, information technology, and communications capabilities. Since then, Biden updated his goal to 

New Data Shows Moderna Vaccine Can Induce Rare Anaphylactic Reactions

According to data by the CDC, Moderna’s COVID-19 vaccine induces rare anaphylactic reactions in a small number of people, similar to that found in recipients of the Pfizer/BioNTech vaccine. Reported by 

, the CDC estimated a prevalence of 2.1 cases of anaphylaxis per million doses of the Moderna vaccine and 6.2 cases per million doses of the Pfizer vaccine.

Fauci: Vaccine Neutralizing Antibodies Lessened by Variants, but Still Likely Effective

The nation’s top infectious disease expert, Anthony Fauci, MD, 

 that current COVID-19 vaccines may be less effective against more contagious variants first identified in South Africa, the United Kingdom, and Brazil, although they will still likely provide enough protection.

Health Officials Nationwide Report Limited Vaccine Supply

The use of Farxiga (dapagliflozin) in addition to standard-of-care therapy in patients with 

 (CKD) not only leads to improved outcomes for patients, but also translates into tens of millions of dollars in lower health care spending for the patient population, according to a new report.

Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor that was initially approved to treat patients with type 2 diabetes (T2D). In 2020, investigators published the results of the 

, which looked at the drug’s impact on renal outcomes and cardiovascular mortality in patients with CKD, with or without T2D.

The results were dramatic. Compared with placebo, patients given the medication saw significant reductions in the incidence of 50% or greater decline in estimated glomerular filtration rate (eGFR), as well as drops in rates of end-stage renal disease (ESRD) and death from renal or cardiovascular causes. The impacts were so dramatic that the study was ended prematurely due to overwhelming efficacy.

Academy of Managed Care Pharmacy’s 2021 meeting

, investigators sought to determine just how this high level of efficacy would impact the cost of care for patients with CKD based on costs of care in the United States. They used event rates from DAPA-CKD to predict the likelihood of those events occurring over a 1-year period. They then used published costs of health care claims to determine the costs of care associated with the patient pool.

The analysis showed that, over the course of a year, treating those patients with dapagliflozin plus standard-of-care therapy would result in 1321 instances of at least a 50% decline in eGFR. By comparison, over the same time period, utilizing only the standard-of-care treatment would see 2414 cases of at least a 50% decline in eGFR (number needed to treat [NNT]: 47).

In terms of ESRD, the analysis suggested that treating patients with dapagliflozin would result in 1271 incidences vs 1919 instances if dapagliflozin were not included in the therapy (a decline of 648 incidences; NNT: 79).

The model showed that 407 hospitalizations for 

 could be avoided using dapagliflozin (410 events with dapagliflozin vs 817 without; NNT: 127) and that 451 fewer deaths would occur in the patient population (1120 vs 1571; NNT: 114).

Those improvements in care would lead to significant cost savings, the investigators found. In a population based on the DAPA-CKD inclusion criteria, health care costs would drop by one-third, or $99.1 million, as a result of dapagliflozin; for those under the age of 65, costs would drop by $121.8 million (37%); and in patients 65 or older, the total costs would drop by an estimated $122.6 million (26%) vs standard of care.

All told, the investigators said the drug would have a significant economic impact if used regularly with the standard of care and if the data from the DAPA-CKD study held true on a population basis.

“Dapagliflozin significantly reduces health care resource utilization in patients with CKD through delayed CKD progression and reduced event incidence, helping to ameliorate the significant burden imposed by CKD on both patients and payers,” they concluded.

McEwan P, Darlington O, Miller R, et al. Translating the findings of DAPA-CKD to reductions in healthcare resource utilization from a U.S. payer perspective. Presented at: Academy of Managed Care Pharmacy 2021; April 12-16, 2021. Abstract N1.

A report using data from the DAPA-CKD study found that dapagliflozin would lead to more than $99 million in savings in a population matched to the trial’s inclusion criteria.

Adding Dapagliflozin to CKD Standard of Care Would Cut Costs by Millions

 since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey. 

Social distancing practices adopted during the COVID-19 pandemic affected both physical activity (PA) levels and sleep quality among 

, according to findings of a multicenter observational study published in 

Changes in nutrition, sleeping habits and psychological distress resulting from the COVID-19 pandemic have been hypothesized to negatively impact individuals’ health and well-being. However, for migraineurs, both well-established genetic factors and external factors have had a known impact on migraine susceptibility.

“Indoor and outdoor environmental factors, including barometric pressure changes, bright sunlight, flickering lights, air quality, and odors, are usually reported as migraine triggers,” researchers wrote. “Additionally, conditions such as shift working, with a consequent disruption of the sleep–wake cycle and increased levels of stress, can contribute to an aggravation of migraine episodes.”

To better understand the impact of social distancing on migraine frequency and severity, and to explore the impact of lockdowns on PA, eating habits and sleep quality on migraineurs, investigators conducted an observational survey consisting of single detailed interviews with patients.

All participants were diagnosed with migraine with or without aura based on the International Classification of Headache Disorders, 3rd Edition, by neurologists, and were aged 18 or older. Data were collected from 261 patients who presented to Italian study centers between May 1, 2020 and July 1, 2020. The social distancing period was considered from March 9, 2020 to May 3, 2020 based on actions by the Italian government.

Patients completed a 4-part questionnaire on migraine characteristics, PA, eating habits and sleep. Migraine patients were classified as "worsened" if their monthly headache frequency increased during social distancing compared with before quarantine. In the opposite case, patients were considered "improved," authors wrote. If frequency of migraine attacks did not change between before and during social distancing, participants were defined as stable.

The majority of study participants (n = 186) had chronic migraine; 87% were female. Mean (SD) patient age was 44.5 (12.3) years. Analyses revealed:

During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency

A significant decrease of PA levels during quarantine was observed in the whole study sample (median total metabolic equivalent task [METs] decreased from 1170 to 510; 

A significant difference was reported on median Insomnia Survey index (ISI) scores (from 7 to 8; 

 < .001), which were increased in patients who presented a stable or worsening headache

The reduction of PA levels was associated with worsening sleep

In addition, migraineurs’ dietary habits were less healthy during lockdown regardless of whether headache worsened, improved, or remained stable. “However, a positive correlation between an increased consumption of healthy foods and walking METs was described in patients who reported a stable headache frequency,” authors wrote. “These results might suggest that healthier dietary and lifestyle habits may have contributed to avoiding migraine worsening during the social distancing.”

Patients’ occupational status was not associated with course of migraine throughout social distancing.

Future studies monitoring PA levels, nutrition and sleep for several months after lockdown in this population could offer new information on the effects of social distancing on migraine.

Di Stefano V, Ornello R, Gagliardo A, et al. Social distancing in chronic migraine during the COVID-19 outbreak: results from a multicenter observational study. 

. Published online April 19, 2021. doi:10.3390/nu13041361

An observational study reveals COVID-19 social distancing measures affected migraineurs' sleep, physical activity. 

Examining the Effects of Social Distancing on Migraine 

The ESMO Breast Cancer Virtual Congress 2021 took place last week, and this Oncology Roundup column highlights a few stories covered by 

ILD Prevention, Detection in Patients on Trastuzumab Deruxtecan for HER2+ Metastatic Breast Cancer

Early detection and optimal management are key in preventing high-grade interstitial lung disease (ILD), a treatment-related adverse effect (AE) of fam-trastuzumab deruxtecan-nxki in patients with HER2-positive metastatic breast cancer, according to retrospective data from a pooled analysis presented during the 

ESMO Breast Cancer Virtual Congress 2021.

 that these patients do not experience cumulative toxicity, as the risk of all-grade ILD fell over time. Notably, toxicity management guidelines for ILD have been updated and implemented since December 2019, in an effort to lower the rates of high-grade ILD through early detection.

Since ILD was identified as an AE of interest in patients receiving trastuzumab deruxtecan, investigators sought to characterize ILD in heavily pretreated patients with metastatic breast cancer. The majority of the events examined took place before the guidelines were implemented; half of the ILD events leading to death were not treated with steroids, as per the guidelines, nor were 40% of the moderate to severe ILD cases.

The analysis is exploratory and hypothesis generating in nature, according to Charles A. Powell, MD, director of the Mount Sinai-National Jewish Health Respiratory Institute and professor of medicine, pulmonary, critical care, and sleep medicine at Mount Sinai. Phase 3 randomized, controlled trials of trastuzumab deruxtecan in breast cancer are ongoing. 

Shorter Duration of Adjuvant Trastuzumab Shows Benefit in Select HER2+ Early Breast Cancer

 confirm the promising long-term results from 9 weeks of adjuvant trastuzumab in patients with HER2-positive early breast cancer who have low and intermediate risk factors, 

®.  That population makes up most patients seen in clinical practice.

After a median follow-up of 8.7 years, patients who received 1 year of trastuzumab had a 5-year disease-free survival (DFS) rate of 87.9% vs compared with 85.8% among those who received it for 9 weeks (HR, 1.09; 90% CI, 0.88-1.35). Moreover, patients had a 5-year overall survival (OS) rate of 95.1% in both arms (HR, 1.18; 90% CI, 0.86-1.62).

Early Study of Datopotamab Deruxtecan in TNBC Shows Promise

The differentiated TROP2-directed antibody-drug conjugate datopotamab deruxtecan (DS-1062a) has a promising antitumor action and a manageable safety profile in heavily pretreated patients with triple-negative breast cancer (TNBC), according to preliminary results from the TNBC cohort of the phase 1 

Among 21 evaluable patients, the objective response rate with datopotamab deruxtecan was 43% (n = 9) per blinded independent central review (BICR); this included a confirmed complete response (CR)/partial response (PR) rate of 24%; 19% of patients also had a CR/PR that was pending confirmation. The disease control rate was 95% by BICR. Only 1 patient experienced disease progression, and no patients discontinued treatment due to AEs.

A roundup of cancer news from the ESMO Breast Cancer Virtual Congress 2021, which took place last week and was covered by OncLive®.

Oncology Roundup: Highlights From the ESMO Breast Cancer Virtual Congress

's parent company, MJH Life Sciences, since 2011. She has an MA in business and economic reporting from New York University.

BK virus (BKV)–associated hemorrhagic cystitis (BKV-HC) is a painful but common complication for patients with leukemia or lymphoma after allogeneic hematopoietic stem cell transplantation (AHSCT). However, BKV-specific T cells from healthy donors may safely and effectively treat BKV-HC.

The results of the phase 2 trial led by researchers at The University of Texas MD Anderson Cancer Center were 

The trial used BKV-specific cytotoxic T lymphocytes (BKV-CTLs) from 26 healthy donors that were banked for off-the-shelf use. Each donor’s blood sample could manufacture anywhere from 20 to 50 doses of antiviral T cells, which can be stored until they are needed. The cells were infused in 59 patients who developed BKV-HC after AHSCT.

The median age of the patients experiencing BKV-HC was 47 years and the most common hematological condition was acute myeloid leukemia. The majority of participants were men (59.3%) and White (55.9%). They received a single infusion and could receive additional infusions every 2 weeks if needed.

The researchers found that 67.7% had an overall response rate (ORR) at day 14. By day 45, the ORR increased to 81.6%. There were no cases of grade 3 or 4 graft-versus-host-disease or other infusion-related toxicities.

“We are extremely encouraged by the safety of this treatment and the rapid responses we’ve seen in the majority of patients,” corresponding author Katy Rezvani, MD, PhD, professor of Stem Cell Transplantation and Cellular Therapy, 

. “Because this approach is so safe, we’ve been able to offer this treatment as an outpatient procedure as soon as patients begin developing symptoms. This has been life-changing for the patients we’ve been able to treat so far.”

The research was done with the support of the MDS and AML Moon Shot, part of the MD Anderson Moon Shots Program, a collaborative effort to rapidly develop scientific discoveries into meaningful clinical advances that save patients’ lives.

The researchers aim to validate the findings of this study in a multi-institutional study.

“Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT,” the authors concluded.

Olson A, Lin R, Marin D, et al. Third-party BK virus-specific cytotoxic T lymphocyte therapy for hemorrhagic cystitis following allotransplantation. 

. Published April 30, 2021. doi:10.1200/JCO.20.02608

BK virus–specific T cells from healthy donors were an effective and safe off-the-shelf treatment for patients with leukemia or lymphoma who developed a painful and common complication after allogeneic hematopoietic stem cell transplantation.

Off-the-Shelf Antiviral T Cells Can Treat Painful Complication After Stem Cell Transplants

As cancer therapies become more targeted, biomarkers are an increasingly important tool to help understand a patient’s individual cancer and identify the treatments that will work best.

For instance, in colorectal cancer, approximately 40% of patients have 

 wild-type disease, and established therapies such as cetuximab and panitumumab are effective, Atrayee Basu-Mallick, MD, a medical oncologist at Sidney Kimmel Cancer Center, and clinical assistant professor at the Thomas Jefferson University, recently told 

On the other hand, approximately 8% of patients with colorectal cancer have a 

 mutation, and the median survival for patients with 

 wild-type disease is only about 13 months. Chemotherapy is not very effective for most of these patients, but they may be able to receive a combination therapy of encorafenib plus cetuximab or encorafenib, cetuximab, and binimetinib.

These combination therapies would not be ideal for patients with HER2-positive disease, though, Basu-Mallick explained. For those patients, trastuzumab plus pertuzumab or trastuzumab plus lapatinib have resulted in more favorable overall response rates.

, Michael Devitt, MD, explained how biomarker-guided therapies are being used in patients with bladder cancer. According to Devitt, hematologist and oncologist and assistant professor at the University of Virginia Medical Center, noted that PD-L1 and 

 are the 2 biomarkers frequently used in bladder cancer.

PD-L1 may identify patients who were ineligible for cisplatin in the frontline setting but may benefit from treatment with carboplatin-based chemotherapy or immunotherapy. Patients with low or no expression of PD-L1 would not benefit from frontline immunotherapy because their response rates to PD-1 inhibitors are low, he explained.

Lastly, new research has identified patients with recurrent ovarian cancer who are more likely to respond to rucaparib. The phase 2 ARIEL2 trial found that 

 promotor methylation are predictive of response to rucaparib. Meanwhile, among patients who were naïve to poly (ADP-ribose) polymerase inhibitors, platinum sensitivity was a strong predictor of response to rucaparib.

In homologous recombination deficiency–associated high-grade ovarian cancer, patients with better outcomes on rucaparib had platinum-sensitive disease and had received fewer lines of prior platinum treatments (1 or 2 prior therapies vs 3 or 4 prior therapies).

Biomarkers are being used in patients with cancer to target treatments that will work best. Interviews with OncLive® highlight how biomarkers are being used in colorectal and bladder cancer.

Precision Medicine Wrap-up: Using Biomarkers to Guide Therapy in Various Cancers

A set of case studies indicates using acitretin (Soriatane) in combination with secukinumab (Cosentyx) may benefit patients with difficult-to-treat psoriasis.

, clinicians in Turkey presented 3 cases showing the potential of acitretin in combination with secukinumab, resulting in nearly complete or total relief.

 and has demonstrated rapid and long-lasting effectiveness in treating moderate-to-severe psoriasis. Yet there are instances where even increasing the dosage fails to provide a clinical response. The most common sites of recalcitrant psoriasis in patients treated with biologics are the anterior lower legs (49.3%), elbows (35.6%), and posterior lower legs (24.7%)

Acitretin is an oral retinoid derived from vitamin A with a history of use alone or in combination with phototherapy. It is the only systemic therapy for psoriasis that is not immunosuppressive, although it is not suitable for in women of childbearing age. It should be used in low doses due to common adverse effects including chapped lips, dryness of the nose and eye, hair loss, and hyperlipidemia.

Methotrexate is used by clinicians in most combination regimens with biologics, the authors said, but acitretin may be a good alternative with lower potential liver toxicity. In the absence of data evaluating the combination of secukinumab and acitretin, the authors presented a case series of patients with different types of psoriasis: chronic plaque, generalized pustular, and erthryrodermic. The patients each had multiple comorbidities and failed to respond to several conventional and biologic therapies, including escalated secukinumab in 2 patients.

The first case was a 64-year-old woman with a 13-year history of chronic psoriasis (PsO) and peripheral psoriatic arthritis (PsA). She also had 

 (T2D), obesity, hypertension, and fatty liver disease complicated by liver fibrosis. The patient had generalized plaque lesions with a score of 29.6 on the Psoriasis Area and Severity Index (PASI) upon initiation of secukinumab at a dose of 300 mg/week for 4 weeks. The authors said skin and joint symptoms improved remarkably, but residual plaques on the forearms and shins persisted despite adding a topical steroid and keratolytic agent.

Within a year, despite significant improvement and a dose escalation of secukinumab, plaques persisted. Four weeks after adding acitretin 25 mg/day (0.3 mg/kg) to secukinumab, the plaques significantly improved without any adverse events. Regression of the lesions continued after 6 months.

The second case was a 37-year-old male with 20-year history of severe chronic PsO accompanied by intermittent erythrodermic attacks. She also had obesity, fatty liver disease, gout, and PSA with axial and peripheral involvement. At week 12, having been treated with 300 mg of secukinumab, his PASI score decreased by 50%-75% (PASI 12). However, at week 16, his PASI score worsened to 17.4. Escalation of the dose to every 2 weeks failed to achieve a response, with infiltrated plaques on the distal extremities persisting. Six weeks of acitretin (25 mg/every other day; 0.1 mg/kg) resulted in significant improvement, and after a year, there were no new lesions or adverse events.

The third case was a 76-year-old male with a 10-year history of chronic PSO and intermittent pustular attacks that often occurred after recurrences of leg cellulitis. He also had T2D, 

, hypertension, atrial fibrillation, obesity, and fatty liver disease.

Acitretin (50 mg/day) was started but discontinued after triple elevations of liver enzymes. After a brief trial of ustekinumab (Stelara), acitretin was reinstated at 25 mg/day; 0.25 mg/kg), yet pustular lesions progressed to widespread plaques. Adding in secukinumab, however, completely cleared the skin at 24 weeks with no side effects. He remained lesion-free after a year.

Polat Ekinci, A, Bölük, KN, Babuna Kobaner, G. Secukinumab and acitretin as a combination therapy for three clinical forms of severe psoriasis in multi‐drug refractory patients: A case series of high efficacy and safety profile. 

. 2021; 34:e14704. doi: 10.1111/dth.14704

Using acitretin in combination with secukinumab resulted in nearly complete or total relief for 3 patients with severe psoriasis, according to a case study.

Patients With Refractory Psoriasis Helped by Combination Therapy, Case Study Finds

Intravitreal dexamethasone implants were found to stabilize, but not improve, 

for most patients with retinal vein occlusion (RVO) even though a majority were pretreated and were receiving the steroid injections as a second-line treatment, a new study showed.

Researchers from Germany targeted the effectiveness of treatment of macular edema (ME), the most frequent vision-threatening consequence of RVO. Most patients previously had been treated with anti-vascular endothelial growth factor (anti-VEGF) agents, with a handful having received intravitreal corticosteroids (triamcinolone).

, found treatment with dexamethasone intravitreal implants (marketed as Ozurex) maintained mean [SD] visual acuity (VA) throughout the observation period (about 10 months on average), with a baseline of 66.7 [23.5] letters and measurements at final observation of 64.9 [28.3]. Central retinal thickness (CRT) saw a reduction from 526 [179] μm at baseline to 431 [199] μm. There was a slight increase in mean intraocular pressure (IOP), rising from 14.4 [3.1] mmHg at baseline to 17.1 [6.3] mmHg.

“Considering the fact that most patients (83%) in this study were not treatment-naïve at the time of first DII treatment, the overall VA results are not surprising,” the researchers said. “Mean VA could be stabilized but did not increase significantly. This may, to a large extent, be contributed to the fact that long-standing or frequently recurring edema has a lower potential for VA increase due to either macular ischemia or structural retinal damage or a combination of both. In this light, it is reassuring that almost one-third of the DII treated eyes were considered a treatment success (ie, having fully resolved macular edemas).”

RVO is the second most common retinal vascular disease after diabetic retinopathy. It is estimated that 16.4 million adults worldwide are affected by RVO and conditions that subsequently develop. The cumulative 10-year incidence was 1.6% in the Blue Mountain eye study of patients 49 and older. ME can be treated with intravitreal injection of anti-VEGF agents or corticosteroids, but when edema is chronic, it poses a challenge to clinicians.

The study evaluated a real-life cohort of 99 eyes from 99 patients with ME due to RVO. Patients were treated between 2011 and 2016 at the University Eye Hospital Freiburg, Germany.

Most eyes were not treatment naïve: 61 eyes (62%) had received anti-VEGF injections prior to DII, 6 (6%) eyes had received triamcinolone, and 15 eyes (15%) had received both. Only 17 eyes (17%) received DII as a first-line treatment. Mean duration of follow-up in the study was 312 [310] days. The number of DII treatments ranged from 1 to 10 with a mean of 2.2 [2.1] injections.

Overall, 47 eyes (47%) did not experience the desired effect and either were stopped from further treatment or switched to other treatments.

Main concerns expressed by the authors were increased IOP and cataract formation. The slight increase translated into a similar increase in usage of intraocular pressure-lowering drops. Over 75% did not require any IOP-lowering therapy during the follow-up period, which was up to 3 years. The IOP returned toward baseline values at later time points. The authors speculated the decrease was because those who showed a significant IOP increase after the first injection frequently did not receive another.

Fifty-eight eyes were phakic at initiation of DII treatment, meaning they were at risk of cataracts. Of those, 13 eyes (22%) received cataract surgery during the follow-up period. Cataract surgery (as well as elevated IOP) occurred less frequently during this study than others.

Intravitreal dexamethasone implants stabilized, but did not improve, vision for most patients with macular edema due to retinal vein occlusion (RVO).