Patients with metastatic breast cancer experienced superior progression-free survival (PFS) after receiving targeted therapy matched to genomic alterations identified through multigene sequencing compared with patients who received maintenance chemotherapy, according to a pooled analysis of findings from the randomized phase 2 SAFIR02_BREAST (NCT02299999) and SAFIR-PI3K (NCT03386162) trials, which were presented during the 2021 San Antonio Breast Cancer Symposium (SABCS).

These trials assessed the impact of multigene sequencing, classified in the I/II tiers of the ESMO Scale of Actionability of Molecular Targets (ESCAT), in consequent targeted therapy.

The results showed that among 115 patients who had an ESCAT I/II genomic alteration, the median PFS was 9.1 months (90% CI, 7.1-9.8) with matched targeted therapy vs 2.8 months (90% CI, 2.1-4.8) with maintenance chemotherapy (adjusted HR, 0.41; 90% CI, 0.27-0.61, 

“These findings suggest that genomics should be a part of the pathway of care, but it has no impact if the results are not interpreted using a validated framework of actionability of the gene alterations identified,” lead study author Fabrice André, MD, PhD, professor of medical oncology at the Institut Gustave Roussy in Villejuif, France, said in a press release, which was accompanied by a virtual press briefing ahead of the conference.

“Multigene sequencing has been widely implemented, but its clinical impact and the best framework for its use are unclear. The main purpose of our study was to test whether genomic analyses are useful for patients with metastatic breast cancer, and how we can best analyze the results,” André said.

To that end, the open-label, multicentric, phase 2 SAFIR02_BREAST and SAFIR-PI3K trials enrolled patients with HER2-negative metastatic breast cancer who were eligible for first- or second-line chemotherapy.

-mutated metastatic breast cancer were randomized to the PI3Kα-specific inhibitor alpelisib (Piqray) plus the estrogen receptor antagonist fulvestrant (Faslodex) or maintenance chemotherapy.

In both trials, patients who had received more than 1 line of chemotherapy or 1 of the targeted therapies evaluated in the trial were excluded from enrollment. If patients had hormone receptor–positive disease, they had to have endocrine-resistant disease.

Patients underwent a pretreatment biopsy of the metastatic lesion, which was followed by next-generation sequencing and SNP array analysis.

After 6 to 8 cycles of induction chemotherapy, patients without evidence of disease progression (n = 238 of 1462; 16%) who had an actionable genomic alteration were randomized to matched targeted therapy (n = 157) or maintenance chemotherapy (n = 81).

The targeted therapy drugs and matching targets consisted of vistusertib for mTOR, AZD4547 for 

, bicalutamide (Casodex) for the androgen receptor, olaparib (Lynparza) for PARP, and alpelisib for 

The primary end point of the study was to determine whether genomically-driven targeted therapy improved PFS vs maintenance chemotherapy.

Hierarchical testing was applied such that efficacy was tested first in patients who had an ESCAT I/II alteration. If a 

 value of less than 0.1 was reported in the first analysis, subsequent analysis was conducted in the intent-to-treat population.

ESCAT classification is defined as follows:

Tier I: Alteration-drug match is associated with improved outcomes in clinical trials

Tier II: Alteration-drug match is associated with antitumor activity, but the magnitude of benefit is unknown

Tier III: Alteration-drug match is suspected to improve outcome based on clinical trial data in other tumor types or with similar molecular alterations

Tier IV: Preclinical evidence of actionability

Tier V: Alteration-drug match is associated with objective response, but without clinically meaningful benefit

Tier X: Lack of evidence for actionability

Additional findings reinforced that ESCAT classification was highly predictive for the benefit of matched targeted therapy (interaction test, 

 = .004). Notably, matched targeted therapy was not effective in patients without an ESCAT I/II alteration (HR, 1.15; 95% CI, 0.76-1.75).

Further findings failed to show a significant difference in PFS between the targeted therapy and chemotherapy arms in the overall population, with a median PFS of 5.5 months (90% CI, 4.0-6.9) vs 2.9 months (90% CI, 2.3-4.8), respectively (adjusted HR, 0.77; 95% CI, 0.56-1.06; 

Additional findings showed that the SNP array analyses (n = 926) detected 21 genes more commonly altered in metastases vs primary tumors. Of these, focal 

amplifications were associated with a poor outcome. Focal 

 amplifications were found after resistance to CDK4/6 inhibitors.

Finally, high homologous recombination deficiency was associated with prolonged PFS in patients with 

 mutations who had received olaparib (HR, 0.32; 95% CI, 0.12-0.83; 

“The general implication of our study is that precision medicine can improve patient outcome if it is interpreted with the right tools,” André said.

“I cannot overstate how important this clinical trial is,” Virginia Kaklamani, MD, a professor of medicine in the Division of Hematology/Oncology at UT Health San Antonio and leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center, and SABCS codirector and moderator of the press briefing added following André’s presentation of the data.

“This is the first trial that we have where we have used genomic alterations to actively change a patient’s treatment plan and found an improvement in the patient’s outcome. This is for early-stage breast cancer patients, which is even more important because the whole point [of treatment] is to try to prevent metastatic disease,” Kaklamani continued.

“What we’re trying to do and what Dr. André showed so eloquently was that by finding changes in the tumor that were unique to that patient and by having targeted therapies available for that change, we were able to treat the patient with that specific targeted therapy instead of standard of care, which would have been chemotherapy, and improve the patient’s outcome. This [tool] is something that we’re going to be using more and more in practice, [so that we’re] really treating our patients based on [their] genomic alterations,” Kaklamani concluded.

André F, Gonçalves A, Filleron T, et al. Clinical utility of molecular tumor profiling: results from the randomized trial SAFIR02-BREAST. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract GS1-10.

Articles

Patients who received matched targeted therapy specific to their genomic alteration, as identified through multigene sequencing, experienced significantly improved progression-free survival. 

Targeted Therapy With Multigene Sequencing Shows Superior PFS Vs Chemotherapy in Metastatic Breast Cancer

Patients with lung cancer, especially patients with minimal serologic response following a second dose of the SAR-SoV2 vaccine, safely experienced seroconversion after receiving a third dose of the vaccine, according to findings from a French study published in the 

The results showed that most patients were immunized after 2 doses and that a third booster shot given to 11% of patients who had persistent low antibody titers induced an 88% immunization rate.

“Though lung cancer patients were reported at high COVID-19-related mortality risk in published series, lethality systematically exceeding 30% of infected patients, we observed only 8 mild COVID-19 cases among our 306 vaccinated patients (2.6%). Such observation strongly supports the efficacy of mRNA COVID-19 vaccines used in 98.4% of our population,” lead study authorValérie Gounant, MD, of the University Hospital Bichat-Claude Bernard in Paris, France, and coauthors wrote in the study publication.

In January 2021, COVID-19 vaccines were made available in France. To increase access to the first vaccine dose, the French Health authorities recommended a 28-day interval for both mRNA vaccines, with a 42-day interval for healthy individuals.

Despite the high COVID-19 mortality rate among patients with lung cancer, the population was excluded from SARS-CoV2 vaccine registration trials, leaving it unknown whether they could develop a protective anti-spike antibody response after vaccination.

As such, investigators conducted a study to evaluate the humoral responses to SARS-CoV2 vaccines in patients with thoracic malignancies.

The prospective study included patients with thoracic cancers who had been seen in Bichat Hospital from January 26, 2021 to July 28, 2021. Patients who had been diagnosed with thoracic cancer and had no known COVID-19 infection within the past 3 months, a life expectancy greater than 3 months, and no known allergies to prior vaccines were contacted and offered vaccination.

The investigators enrolled and vaccinated 306 patients with lung cancer. Most patients were male (n = 181; 59.2%) and had lung cancer (n = 285; 93.1%); 260 patients (84.9%)

had non–small cell lung cancer and 22 (7.2%) had small cell lung cancer, while 13 patients (4.4%) had pleural malignant mesothelioma. Patients were a median age of 67 years (interquartile range, 58-74), and the majority (n = 283) had received 2 vaccine doses at 28-day intervals.

The last treatment patients received within 3 months before their first vaccine dose was chemotherapy (n = 74; 24.2 %) alone (n = 51; 16.7%), with concurrent radiotherapy (n = 2), or combined with a checkpoint inhibitor (n = 21; 6.9%); 49 patients (16%) received a checkpoint inhibitor alone, and 13.7% were treated with daily TKIs or maintenance bevacizumab (Avastin). The last 141 patients (30.7%) had not received systemic treatment within the last 3 months leading up to vaccination.

The primary end point was the humoral immunity against SARS-CoV-2-spike following the COVID-19 mRNA BNT162b2 vaccine injection and booster dose. Some patients were vaccinated outside the center and received the Moderna mRNA-1273 (n = 1) or AstraZeneca ChAdOx1 nCov-19 (n = 3) vaccines.

SARS-CoV2-spike antibodies were measured with the Abbot ARCHITECT SARS-CoV-2 IgG immunoassay before the first injection of the mRNA vaccine, after the fourth week, and 2 to 16 weeks after second vaccine dose.

After a median follow-up of 6.7 months, 8 patients (2.6%) had developed symptomatic SARS-CoV-2 infection, with a fast-onset evolution. Of 269 serological results that had been collected after 14 days following the second vaccine dose, 17 (6.3%) were still negative (<50 arbitrary units [AU]/mL), and 34 (11%) were less than 300 AU/mL in the 12.5th percentile—the level at which an exact correlation was found between anti-S antibodies and neutralizing antibodies.

Multivariate analysis demonstrated that age, chemotherapy as the last systemic treatment within 3 months, and chronic corticosteroid treatment were significantly associated with a lack of immunization.

Thirty patients received a third vaccine dose, after which 3 patients showed persistent negative serology and the rest seroconversion.

In terms of safety, data were available for most patients (n = 278; 90.1%), without significant safety concerns.

One-third of patients (n = 98) did not report symptoms following their first injection. Reported adverse effects (AEs) included transitory pain, injection-site swelling, or grade 1 injection-site erythema lasting less than 24 hours.

AEs were reported in 201 patients following the second dose and included injection-site erythema, pain, local injection-site swelling, mild fever (< 38.5°C) all lasting less than 36 hours. Flu-like symptoms, chills, and fatigue lasting less than 48 hours were reported in 25 (8%) cases.

Additionally, no anaphylaxis reaction was reported following the administration of 587 vaccine doses.

“Although this report involves, to the best our knowledge, the largest series of patients [with thoracic cancer] receiving anti-SARS-CoV-2 mRNA vaccines that has been published to date, the sample size of the different patient subsets remains limited,” the authors concluded.

Gounant V, Ferre VM, Soussi G, et al. Efficacy of SARS-CoV-2 vaccine in thoracic cancer patients: a prospective study supporting a third dose in patients with minimal serologic response after two vaccine doses. 

COVID-19 vaccine effective in patients with lung cancer results from a French study published in the Journal of Thoracic Oncology. News release. IASLC. November 16, 2021. Accessed November 19, 2021. https://bit.ly/3HCNZdX

This article was originally published on OncLive as “Third SARS-CoV2 Vaccine Shows Evidence of Seroconversion in Lung Cancer”

A study in France showed that patients with lung cancer, a population initially excluded from COVID-19 vaccination registration trials, were able to safely receive 3 doses. 

Third COVID-19 Vaccine Dose Effective and Safe in Patients with Lung Cancer

Identifying prognostic markers in patients with chronic lymphocytic leukemia (CLL) at diagnosis is critical, explained Deborah M. Stephens, DO. Findings from these biomarker tests allow for personalized therapy options, help identify patients eligible for clinical trials, and can be used to educate patients on their prognosis.

The clinical presentation of CLL is heterogeneous. Some patients can receive active surveillance for a period before starting therapy, whereas others require immediate treatment. Prognostic factors, such as immunoglobulin variable heavy chain (

), fluorescence in situ hybridization (FISH), and 

, can indicate whether a patient has more aggressive or indolent disease and inform whether a traditional chemoimmunotherapy regimen, such as fludarabine, cyclophosphamide, and rituximab (Rituxan; FCR), or targeted therapy is more appropriate.

“In CLL, we really do have to consider both clinical risk and molecular risk,” said Stephens, director of the CLL and Lymphoma Program at Huntsman Cancer Institute, in a presentation on the evolving role of prognostic markers in CLL in the era of novel agents during the 39th Annual Chemotherapy Foundation Symposium Innovative Cancer Therapy for Tomorrow® (CFS®), a program hosted by the Physicians’ Education Resource® (PER®), LLC.

Association Between Prognostic Factors and Targeted Therapy Benefit

 status can influence whether to recommend targeted therapy, explained Stephens.

“I have a very strong preference for using targeted therapy in patients with unmutated 

,” said Stephens, who is also an assistant professor within the Division of Hematology and Hematologic Malignancies at the University of Utah.

The marker itself represents DNA sequencing for homology to the most similar germline gene; if the gene has at least 98% homology, 

, which comprise approximately 50% of the CLL population, have a median overall survival (OS) of approximately 9 years vs approximately 25 years in patients with mutated IGHV.

“A good thing about this risk factor is that it doesn’t change over time, so you can check 

 is important to evaluate, Stephens cited the phase 3 EA1912 trial (NCT02048813), which evaluated frontline ibrutinib (Imbruvica) plus rituximab vs FCR. The study showed that among patients with unmutated IGHV, the 3-year progression-free survival (PFS) rate was 90.7% with ibrutinib/rituximab vs 62.5% with FCR (HR, 0.26; 95% CI, 0.14-0.50), indicating that the ibrutinib-based therapy was far superior to chemoimmunotherapy in patients with the poor-risk marker.3

Similarly, the results of the phase 3 CLL14 trial (NCT02242942), which evaluated the frontline combination of venetoclax (Venclexta) and obinutuzumab (Gazyva) vs chlorambucil and obinutuzumab, showed an improvement in PFS with venetoclax/obinutuzumab vs chlorambucil/obinutuzumab, regardless of 

 The findings indicate that targeted agents are favored drugs for patients with unmutated 

-unmutated and -mutated patients, the venetoclax arms did exactly the same,” said Stephens. “

 status is very important in the likelihood and timing of treatment, and 

 can be used to tailor the frequency of clinic visits,” said Stephens.

FISH testing has been around for some time, said Stephens, explaining that it’s used to probe for common and significant mutations in CLL, including deletion 13q, trisomy 12, deletion 11q, and deletion 17p, the latter of which is associated with particularly poor prognosis. Notably, FISH can change over time and should be reevaluated at the time of subsequent therapy.

With ibrutinib monotherapy, patients with deletion 17p had a median PFS of approximately 3 years vs approximately 1 year with chemoimmunotherapy in the phase 3 CLL-8 trial (NCT00281918).5,6

In the CLL14 trial, patients without deletion 17p had improved PFS regardless of whether they received venetoclax/obinutuzumab or chlorambucil/obinutuzumab (HR, 4.42; 

 < .01, respectively).4 However, venetoclax/obinutuzumab is still favorable vs chlorambucil/obinutuzumab, regardless of mutational status, said Stephens.

Stephens also addressed deletion 11q, which has historically been a poor prognostic marker. However, in a meta-analysis of 3 randomized studies of ibrutinib vs a comparator, the 42-month PFS rate was prolonged in patients with deletion 11q vs without, at 70% vs 65%, respectively (

“The authors suggested that deletion 11q should no longer be considered an adverse prognostic factor when patients are treated with ibrutinib,” Stephens said.

 aberrations, or tumor suppressor proteins, are often associated with deletion 17p and are found in approximately 10% of patients with CLL at diagnosis, said Stephens.

 mutation had improved PFS regardless of whether they received venetoclax/obinutuzumab or chlorambucil/obinutuzumab (HR, 3.08; 

 However, because patients with the aberration have poor PFS with standard chemoimmunotherapy and improved PFS with both ibrutinib and venetoclax/obinutuzumab, Stephens stated that either targeted approach would be better than chemoimmunotherapy in these patients.

Also associated with these aberrations is complex karyotype, which is defined as more than 3 abnormalities. Complex karyotype is currently associated with poor prognosis, even in ibrutinib-treated patients. However, a recent analysis indicated that the definition should be amended after the results showed that at least 5 chromosomal aberrations were found to be a novel, independent prognosticator.8

“These chromosomal abnormalities are highly inter-related and have a high impact on survival, [which has led to my] strong preference for targeted therapy in these patients,” Stephens said.

Combining Molecular Risk With Clinical Risk

The CLL International Prognostic Index (CLL-IPI) combines molecular risk factors like deletion 17p and TP53 and IGHV status with clinical risk factors, such as age and Rai stage, to determine whether a patient has low-, intermediate-, high-, or very high–risk disease. The tool is helpful not only in understanding a patient’s survival probability, but also in estimating their time to first treatment.

According to a paper published in Lancet Oncology, the CLL-IPI model estimated that the 5-year OS rates of patients with low-, intermediate-, high-, or very high–risk disease were 91%, 80%, 53%, and 19%, respectively.

 The 10-year OS rates were 87%, 40%, 16%, and 0%, respectively.

Regarding time to first treatment, a study published in the American Journal of Hematology indicated that, when stratified by low-, intermediate, and high-risk according to the CLL-IPI, the 5-year time to first treatment rates were 75%, 39%, and 23%, respectively.

In conclusion, Stephens highlighted the ongoing phase 3 EVOLVE CLL Study/SWOG 1925 trial (NCT04269902) as a potential clinical trial for asymptomatic patients with newly diagnosed CLL who undergo molecular testing and are found to have a CLL-IPI score of at least 4, and/or complex cytogenetics. The study is evaluating early vs delayed treatment with venetoclax and obinutuzumab. Patients will be stratified by high-risk vs very high–risk CLL.

“This trial is a great benefit to patients because, in both of these arms, the drugs are completely paid for and [the results] will answer an important question of whether these high-risk patients should be treated early,” Stephens concluded.

Stephens DM. The evolving role of prognostic markers for CLL in the era of novel agents: putting data to practice. Presented at: 

Hamblin TJ, Davis Z, Gardiner A, et al. Unmutated Ig VH genes are associated with a more aggressive form of chronic lymphocytic leukemia. 

. 1999;94(6):1848-1854. doi:10.1182/blood.V94.6.1848

Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. 

 2019;381(5):432-443. doi:10.1056/NEJMoa1817073

Tausch E, Schneider C, Robrecht S, et al. Prognostic and predictive impact of genetic markers in patients with CLL treated with obinutuzumab and venetoclax. 

. 2020;135(26):2402-2412. doi:10.1182/blood.2019004492

Byrd JC, Furman RR, Coutre SE, et al. Ibrutinib treatment for first-line and relapsed/refractory chronic lymphocytic leukemia: final analysis of the pivotal phase Ib/II PCYC-1102 study. 

. 2020;26(15):3918-3927. doi:10.1158/1078-0432.CCR-19-2856

Stilgenbauer S, Schnaiter A, Paschka P, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. 

. 2014;123(21):3247-3254. doi:10.1182/blood-2014-01-546150

Kipps TJ, Fraser G, Coutre SE, et al. Long-term studies assessing outcomes of ibrutinib therapy in patients with del(11q) chronic lymphocytic leukemia. 

. 2019;19(11):715-722. doi:10.1016/j.clml.2019.07.004

Baliakas P, Jeromin S, Iskas M, et al. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. 

. 2019;133(11):1205-1216. doi:10.1182/blood-2018-09-873083

International CLL-IPI Working Group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. 

. 2016;17(6):779-790. doi:10.1016/S1470-2045(16)30029-8

Molica S, Shanafelt TD, Giannarelli D, et al. The chronic lymphocytic leukemia international prognostic index predicts time to first treatment in early CLL: Independent validation in a prospective cohort of early stage patients. 

. 2016;91(11):1090-1095. doi:10.1002/ajh.24493

This article was originally published on OncLive as “Testing for Prognostic Markers Is a Necessity for Optimized CLL Care”

Findings from biomarker tests for patients with chronic lymphocytic leukemia can help appropriately tailor therapy plans as well as identify patients eligible for clinical trials. 

Optimized CLL Care Requires Prognostic Marker Testing at Diagnosis

Findings from a research letter published in 

 demonstrate that the number of pancreatic cancer incidences increased overall between 2000 and 2018.

 Moreover, the number of cases among woman younger than 55, particularly between 15 to 35 years, grew significantly.

The results showed a significant increase in the average annual percentage changes of the total pancreatic cancer cases in women (0.78%; 95% CI, 0.68%-0.88%; 

 <.001) and in men (0.90%; 95% CI, 0.82%-0.99%; 

 <.001). There was no statistically significant difference between sexes (0.12%; 95% CI, 0%-0.25%; 

The incidence rates were considerably lower among the 32,369 patients younger than 55 years (11.4% of cases; 43% women). However, the data showed a greater relative increase in incidence among women younger than 55 years (1.93%; 95% CI, 1.57%-2.28%; 

 < .001) vs men in the same age category (0.77%; 95% CI, 0.50%-1.05%; 

 < .001), indicating nonequal trends (

“These findings are important because this is the first time, using the most current data, that we are reporting that pancreatic cancer rates are increasing dramatically in women who are younger than 55,” lead study author and assistant professor of medicine at Cedars Sinai, Srinivas Gaddam, MD, said in a press release.

 “The findings are most dramatic in women less than 35 years old.”

Pancreatic cancer is the fourth leading cause of cancer-related mortality with a 5-year survival rate of approximately 10%. Noncomparative data from 2013 showed a rising increasing incidence of pancreatic cancer in older White women and men and in younger non-Hispanic White women. However, limited data exist regarding current patterns in pancreatic cancer incidence. As such, Gaddam and colleagues conducted an age- and sex-specific time trend analysis of pancreatic cancer incidence rates.

Pancreatic cancer incidence rates per 100,000 population were collected from 2000 to 2018 from the Surveillance Epidemiology and End Results database. A total of 283,817 diagnoses were recorded in the database, 50% which occurred in women. These data were age-adjusted to the 2000 United States population and adjusted for the reporting delay.

Patients younger than 55 years were termed younger adults and those aged 55 years or older were termed older adults. Investigators also conducted post-hoc analysis for patients aged the 15 to 34 years and for those aged 35 to 54 years.

Further results demonstrated that, among patients aged 55 years or older (n = 251,360; 51% women), the average annual percentage changes increased among women (0.62%; 95% CI, 0.51%-0.74%; 

 <.001) but more so in men (0.92%; 95% CI, 0.82%-1.01%; 

 < .001), reflecting nonequal trends (

To better understand the pattern reversal, the cohort of patients under the age of 55 years was split into 2 subgroups: 35 to 54 years (n = 30,831; 10.9%) and 15 to 34 years (n = 1538; 0.54%).

Women aged 35 to 54 years had a greater relative increase in incidence rates (n = 13,139; average annual percentage change, 1.56%; 95% CI, 1.24%-1.87%; 

 <.001) compared with men (n = 17,692; average annual percentage change, 0.65%; 95% CI, 0.38%-0.91%; 

 <.001). Investigators also reported nonequal trends (

Women aged 15 to 34 years also had a greater relative increase (n = 896; average annual percentage change, 7.68%; 95% CI, 6.21%-9.18%; 

 <.001) vs men (n = 642; average annual percentage change, 4.20%; 95% CI, 2.54%-5.90%; 

 <.001), again demonstrating nonequal trends (

“We don’t know the causes yet. Women with abdominal pain should not run to their primary care physicians and ask for a CT scan,” Gaddam said. “The incidence of this cancer is still very low in young people. We’ve identified this risk because we want to know what’s causing the significant upward trend. Also, are we catching it early? Will it continue for decades to come? Our goal is to find the answers to those and other questions.

“Future studies should validate these findings in other large population-based cohorts,” Gaddam concluded.

Gaddam S, Abboud Y, Oh J, et al. Incidence of pancreatic cancer by age and sex in the US, 2000-2018. 

. Published online October 24, 2021. Accessed October 29, 2021. doi:10.1001/jama.2021.18859

Study: incidence of pancreatic cancer rising in younger women. News release. Cedars Sinai. October 25, 2021. Accessed October 29, 2021. https://ceda.rs/3pPL9M0

This article was originally published on OncLive as “Pancreatic Cancer Incidence Rises, Notably Among Younger Women”

Between 2000 and 2018, the number of pancreatic cancer cases rose, particularly among women between the ages of 15 to 35 years.

 Pancreatic Cancer Cases Climbing, Especially in Younger Women

Findings from a retrospective analysis published in the 

 revealed that patients with polycythemia vera are not at an increased risk of secondary malignancies after receiving ruxolitinib (Jakafi).

The results demonstrated that no significant difference was identified between the number of patients with polycythemia vera with ruxolitinib-associated secondary malignancies (n = 10; 41.7%) and the patients (n = 14; 58.3%) who developed secondary malignancies without ruxolitinib (

“Our data do not show an increased risk of secondary malignancies, particularly lymphoma, in polycythemia vera patients treated with ruxolitinib. Therefore, in high-risk polycythemia vera patients with hydroxyurea intolerance or resistance, concern about developing secondary malignancies does not appear to be a major factor preventing ruxolitinib therapy,” wrote lead study author Rohit Sekhri, of the University Clinic for Hematology, Oncology, Hemostaseology and Palliative Care at Johannes Wesling Medical Center Minden, and coauthors in the study publication.

Ruxolitinib has drawn attention because of its risk for secondary malignancies in patients with myelofibrosis. However, data regarding the risk of secondary malignancies in patients with polycythemia vera treated with the JAK1/2 inhibitor are few and far between.

As such, investigators sought to evaluate the relationship between treatment with ruxolitinib in polycythemia vera and secondary malignancies.

The single-center study comprised 289 patients with 

 V617F–mutated polycythemia vera who had been diagnosed according to the World Health Organization 2016 criteria. The enrollment period began on May 14, 2013; data cutoff was December 1, 2020.

Regarding patient demographics, most patients were women (58.8%). At the time of diagnosis, more than half of patients (52.2%) were between 40 and 60 years of age and had low-risk disease (50.5%) according to their polycythemia vera survival score.

Additional results indicated that the median duration of cytoreductive therapy for polycythemia vera was 73.5 months (range, 1.0-311.0).

Most patients received hydroxyurea (n = 185; 64.0%) for a median duration of 45.2 months (range, 0.2-289.0) followed by ruxolitinib, which was given to 32.9% (n = 95/289) of patients for a median duration of 48.0 months (range 1.0-101.6).

At a median follow-up of 97 months (range, 1.0-395.0) following polycythemia vera diagnosis, 24 (8.3%) secondary malignancies were recorded.

The median time to development of the secondary malignancy was 7.2 years (range, 0.1-22.9) after polycythemia vera diagnosis, and the median age at secondary malignancy diagnosis was 69.7 years (range, 29.6-89.5).

Most of the secondary malignancies (n = 9/24; 37.5%) were reported in patients with intermediate-risk disease.

Notably, no increased cases of melanoma (

 = .60), or solid non-skin malignancies (

 = .63, all chi square test) were reported with ruxolitinib.

However, a substantial proportion of non-melanoma skin cancer was seen with ruxolitinib treatment vs without (n = 11; 45.8%; 

The secondary malignancy–free survival was comparable by log rank test for all 289 patients (

 = .65), for the patients (n = 208; 72%) receiving cytoreductive therapy (

 = .48) or for different treatment sequences (

In multivariate analysis, advanced age at polycythemia vera diagnosis (HR, 1.062; 95% CI, 1.028-1.098) but not treatment with ruxolitinib (HR, 1.068; 95% CI, 0.468-2.463) was associated with an increased risk for secondary malignancies (

“Our data indicate an increased risk of non-melanoma skin cancer with ruxolitinib therapy, especially in the case of hydroxyurea pretreatment. Therefore, in the future, the evolution of such malignant skin lesions in polycythemia vera patients treated with ruxolitinib should be identified at an early stage by regular dermatological monitoring,” concluded the study authors.

Sekhri R, Sadjadian P, Becker T, et al. Ruxolitinib-treated polycythemia vera patients and their risk of secondary malignancies. 

. 2021;100(11):2707-2716. doi:10.1007/s00277-021-04647-0

This article was originally published on OncLive as “Ruxolitinib Found Not to Increase the Risk for Secondary Malignancies in Polycythemia Vera”

Ruxolitinib was not associated with an increased risk of secondary malignancies in patients with polycythemia vera.

Ruxolitinib for Polycythemia Vera Not Associated with Increased Secondary Malignancy Risk 

Patients with soft tissue sarcoma who experienced wound complications following preoperative and postoperative radiation therapy reported higher levels of anxiety and decreased physical function than those without these complications into the Patient Reported Outcomes Measurement Information System (PROMIS), suggest results from a study published in 

Clinical and Translational Radiation Oncology

The results showed that patients with wound complications were more likely to have a significant increase in anxiety (36.4% vs 8.3%; 

 = .020) and a significant decrease in physical function (57.1% vs 16.2%; 

 = .011) independent of the timing of radiation therapy.

“This study demonstrates minimum significant change thresholds to detect PROMIS changes in soft tissue sarcoma patients undergoing pre- and postoperative radiotherapy. As expected, more patients with preoperative radiation therapy than postoperative radiation therapy had wound complications, but patients with complications in both groups had worse anxiety and function at the completion of treatment compared with those that did not,” wrote lead study author T.M. Moon, MD, of Washington University in St. Louis, and coauthors, in the study publication.

Wide surgical excision and radiation therapy is the recommended local treatment for patients with high-risk soft tissue sarcoma of the extremities. However, the determination of whether to give radiation therapy pre- or postoperatively remains a challenge.

Preoperative radiation therapy can cause a reduced risk of late complications, such as fibrosis and joint stiffness. However, it can also cause an increased risk of significant wound complications that can reduce short-term postoperative function.

Furthermore, few studies in the modern era have evaluated patient-reported outcomes (PROs) during pre- and postoperative radiation therapy for soft tissue sarcoma, and none have used PROMIS, a scoring system which is favored over historical PRO measures and is endorsed by the National Cancer Institute.

Therefore, PROMIS scores were evaluated across perioperative timepoints for patients receiving pre- or postoperative radiation therapy.

All patients included in the study were over the age of 18 years who underwent surgical treatment for primary or repeat surgical resection of a malignant soft tissue sarcoma and had been evaluated in an orthopedic oncology clinic between July 1, 2015, and October 31, 2019.

Radiation therapy was given using 3D conformal or intensity-modulated radiotherapy. Preoperative radiation therapy was dosed between 50 Gy to 50.4 Gy in 25 to 28 fractions with a postoperative boost for positive margins, and postoperative radiation therapy was dosed between 60 Gy to 66 Gy in 30 to 33 fractions. No patients who received preoperative radiation were given postoperative radiation if the margins were positive after surgery.

Anxiety, depression, pain interference, and physical function PROMIS domains were collected preoperatively, immediately postoperatively, and following treatment completion.

Median scores were compared between groups using the Kruskal-Wallis test. The reliable change index (RCI) was used to determine the minimum important change in PROMIS scores and to compare scores between timepoints.

A total of 95 patients were included (n = 19 preoperative; n = 76 postoperative). No significant differences were reported in demographic, surgical, or pathologic data apart from gender between the preoperative (21.1%, female; 78.9%, male) and postoperative (46.1%, female; 53.9%, male) groups (

Incomplete PROMIS data left a total of 89, 93, and 53 patients eligible for analysis in the preoperative, immediate postoperative, and end of treatment cohorts, respectively.

Both cohorts had a significant decrease in function during treatment.

Anxiety scores were significantly lower at the posttreatment completion timepoint vs the other 2 timepoints (effect size −5.91; 

 = .0015). None of the variables were significantly associated with depression scores at any timepoint, and they were similar across timepoints.

The physical function scores were also significantly lower at the immediate postoperative timepoint vs the other 2 timepoints (effect size – 6.94; 

Patient Reported Outcomes Measurement Information System scoring suggested that wound complication was associated with more severe anxiety and decreased physical function in patients receiving radiation therapy for soft tissue sarcoma. 

Caroline Seymour

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