 
Courtney Marabella joined the MJH Life Sciences team in 2021 and is Senior Editor for 

. Prior to joining the company she worked as the Audience Development Editor for the Asbury Park Press, part of the USA Today Network. 

The NeoADAURA trial (NCT04351555) will evaluate the safety and efficacy of neoadjuvant osimertinib (Tagrisso), as a single agent or in combination with platinum-based chemotherapy compared with chemotherapy alone, in patients with resectable, stage II-IIIB non–small cell lung cancer (NSCLC) whose tumors harbor 

mutations, according to data presented at the International Association for the Study of Lung Cancer 2020 

The primary end point of the study is focused on evaluating major pathological response (MPR), which is defined as less than or equal to 10% of residual cancer cells in the lung tumor specimen following surgery per central assessment. The study sample was based on approximately a 90% power to identify a statistically significant 20 percentage point difference in MPR, with a 2-sided overall significance level of 5% when assuming a 20% MPR in the control arm.

One interim futility analysis will be performed based on MPR, the smallest treatment effect of absolute difference of 6% versus the control arm, will be performed; this will happen after approximately half of the study participants have undergone surgery.

Key secondary end points for the study include event-free survival, pathological complete response, downstaging, disease-free survival (DFS), overall survival (OS), MPR in patients with or without detectable 

mutations in plasma circulating tumor DNA at screening, disease-related symptoms and health-related quality of life, as well as safety and tolerability.

About 30% of patients with NSCLC present with resectable disease, and the primary treatment for this population is curative surgery; however, prognosis after surgery continues to be poor. Neoadjuvant or adjuvant chemotherapy is recommended for certain patients with resectable stage 3 disease, irrespective of 

status, as this has been proven to have clinical benefit.

For example, results from a prior phase 3 study showed that preoperative chemotherapy significantly improved outcomes for patients with stage IIB/IIIA NSCLC compared with surgery alone. The progression-free survival (PFS) rate at 3 years was 36.1% with preoperative chemotherapy versus 55.4% with surgery alone (

 = .002). However, improved treatment options for patient with stage 2-3 disease are still needed, as the 5-year probability for OS is 65% for those with stage IIA disease, 56% for those with stage IIB disease, 41% for stage IIIA disease, and 24% for stage IIIB disease.

The third-generation, irreversible EGFR TKI osimertinib was developed to inhibit 

 sensitizing mutations and T790M resistance mutations, as well as to have central nervous system (CNS) activity. In the pivotal phase 3 ADAURA trial (NCT02511106), the agent resulted in a statistically significant improvement in DFS at 24 months (HR, 0.20; 99.12% CI, 0.14-0.30; 

December 2020 FDA approval of osimertinib for use as an adjuvant treatment

 following tumor resection in patients with NSCLC whose tumors harbor 

 exon 19 deletions or exon 21 L858R mutations. Moreover, updated data presented during the 

EGFR TKI reduced the risk for CNS death or progression by 82%

Recent studies have suggested that treatment with an EGFR TKI treatment could be feasible in the neoadjuvant setting in that it could potentially result in reduced tumor burden and eliminate micrometastases.

“Combining an EGFR TKI and chemotherapy in the neoadjuvant setting may optimize tumor downstaging and micrometastatic eradication,” the NeoADAURA authors wrote in the poster. “In advanced disease, combining an EGFR TKI with chemotherapy has resulted in improved PFS versus EGFR TKI [monotherapy].”

Additionally, results from a recent phase 2 study (NCT03433469) indicated that neoadjuvant osimertinib was well tolerated in patients with stage I-IIIA NSCLC. Participants went to surgical resection without experiencing any unscheduled delays.

Because of the favorable efficacy and tolerability data that have been reported with osimertinib in the advanced and adjuvant settings, investigators have set out to examine the agent in the neoadjuvant setting for patients with resectable disease.

The randomized, controlled, multicenter NeoADAURA trial will enroll a total of 351 patients with resectable, stage II-IIIB NSCLC whose tumors harbor 

 mutations. Participants will be stratified by disease stage (II vs III), ethnicity (non-Asian vs Chinese vs other Asian), and type of 

 mutation (exon 19 deletion or L858R deletion).

To be eligible for enrollment, patients have to be aged 18 years and have primary nonsquamous stage II-IIIB N2 NSCLC with 

mutations confirmed on their baseline tumor biopsy sample, or primary NSCLC that has been deemed to be completely resectable by a multidisciplinary team, including a thoracic surgeon. Patients must also have an ECOG performance status of 0-1, acceptable organ and bone marrow function, and a life expectancy of greater than 6 months prior to randomization.

If patients previously received systemic therapy for their disease, had mixed small cell and NSCLC histology, underwent preoperative radiotherapy, or had bulky N2 disease, they could not participate. Moreover, patients who were candidates for segmentectomies or wedge resections only were also excluded. If they had T4 tumors infiltrating the aorta, esophagus, and/or heart; a history of, or current, interstitial lung disease (ILD), drug-induced ILD, or radiation pneumonitis; severe or uncontrolled systemic diseases or active infections; a history of allogeneic organ transplantation, primary immunodeficiency, or another primary malignancy, among other criteria; they could not participate.

Patients will be randomized 1:1:1 to receive either daily placebo plus investigator’s choice of pemetrexed at 500 mg/m

 plus carboplatin AUC5 mg/ml/min or cisplatin at 75 mg/m

given in 3 cycles every 3 weeks; osimertinib at a daily dose of 80 mg plus investigator’s choice of pemetrexed plus carboplatin or cisplatin at the same dosing schedule or osimertinib at a daily dose of 80 mg for 9 weeks. The first 2 arms will be double-blinded, while the third arm will be open-label, sponsor-blind.

After patients received treatment, they will go on to undergo surgery, be evaluated for MPR and pCR, and then go on to receive adjuvant treatment with investigator’s choice of therapy. Participants will be followed for OS for 5 years after surgery. Investigators will evaluate patients 12 weeks and 24 weeks following surgery, and then every 24 weeks thereafter, until disease recurrence or consent is withdrawn. Notably, osimertinib will be offered to all patients who complete surgery, with or without post-surgical chemotherapy, for up to 3 years, or until disease recurrence.

In the trial, investigators will also evaluate health resource use by utilizing the EQ-5D-5L health state utility index and metabolic response per PERCIST criteria. They will also evaluate genetic, gene expression, and proteomic markers, as well as examine the relationship between molecular evidence of disease and clinical response end points. Other exploratory end points of the trial include evaluating the relationship between molecular aberrations and response and learning more about human leukocyte antigen alleles linked with susceptibility to drug-related adverse effects.

Enrollment for the NeoADAURA trial began in December 2020. The trial will be available in 23 countries including the United States, Mexico, Brazil, Austria, Germany, Italy, the United Kingdom, Russia, China, India, South Korea, and Vietnam. Data from the prior MPR analysis are anticipated to be available in 2024.

Tsuboi M, Weder W, Escriu C, et al. Neoadjuvant osimertinib with/without chemotherapy vs chemotherapy for EGFR mutated resectable NSCLC: NeoADAURA. Poster presented at: 2021 World Conference on Lung Cancer Singapore; January 28-31, 2020; Singapore. Accessed January 28, 2021. 

Wu Y-L, Tsuboi M, He J, et al. Osimertinib in resected 

. 2020;383(18):1711-1723. doi:10.1056/NEJMoa2027071

Tsuboi M, Wu Y-L, He J, et al. Osimertinib adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) NSCLC (ADAURA): central nervous system (CNS) disease recurrence. 

. 2020;31(suppl 6):S1378. doi:10.1016/j.annonc.2020.10.349

Articles

January 28, 2021 - The NeoADAURA trial will evaluate the safety and efficacy of neoadjuvant osimertinib, as a single agent or in combination with platinum-based chemotherapy compared with chemotherapy alone, in patients with resectable, stage II-IIIB non–small cell lung cancer whose tumors harbor EGFR mutations.

NeoADAURA Trial Slated to Examine Neoadjuvant Osimertinib in Resectable EGFR+ NSCLC

The combination of the polo-like kinase 1 (PLK1) inhibitor, onvansertib, with FOLFIRI and bevacizumab (Avastin) was found to have preliminary activity and favorable tolerability when used as a second-line treatment for patients with 

-mutated metastatic colorectal cancer (mCRC), according to results from a phase 1b/2 study (NCT03829410) presented during the virtual 2021 Gastrointestinal Cancers Symposium.

Forty-two percent of patients (n = 5) evaluated achieved a partial response (PR) with the regimen, including 4 confirmed PRs. Moreover, 1 of these patients went on to receive curative surgery. Sixty-seven percent of patients (n = 8) experienced durable responses that ranged from 6 months to 13 months. Because the combination was found to be well tolerated, the dose level of 15 mg/m2 will be examined further as the recommended phase 2 dose (RP2D).

“Clinical responses were observed across different 

 variants, including the most common mutations [in CRC]. Patients [who] achieved a PR showed the greatest decrease in plasma mutant 

 after 1 cycle of therapy,” lead study author Daniel H. Ahn, DO, consultant in the Division of Hematology/Oncology of the Department of Internal Medicine at Mayo Clinic, said during an oral presentation of the data. “Phase 2 of the study will further assess the safety and efficacy of onvansertib in combination with FOLFIRI and bevacizumab, as well as [evaluate] the value of 

 assessment through liquid biopsy to predict treatment response.”

 is mutated in approximately 50% of patients with CRC, and RAS-targeted therapies have failed, with most of 

 mutations considered to be “undruggable,” noted Ahn. As such, effective second-line options are needed for these patients, where the median overall survival (OS) is less than 12 months, with an overall response rate of about 5% and a progression-free survival (PFS) of 5.7 months.

PLK1 is a key regulator of mitosis and is overexpressed in CRC; this overexpression is linked with a poor clinical prognosis. PLK1 inhibition has been found to have synthetic lethality with mutant 

 in CRC cells. Onvansertib, an oral and highly selective PLK1 inhibitor, has demonstrated synergistic and antitumor activity when used in combination with irinotecan and 5-fluorouracil (5-FU) in 

-mutated xenograft mouse models; this provided the preclinical rationale for the study presented during the meeting, according to Ahn.

To be eligible for enrollment on the trial, patients had to have metastatic and unresectable CRC, 

 mutations in the primary tumor or metastasis, have progressed on or were intolerant to oxaliplatin-based chemotherapy, and who experienced disease progression on less than 6 months of first-line therapy. Patients had to be negative for 

 V600E mutation and microsatellite instability high/deficient mismatch repair status.

In phase 1b portion of the trial, onvansertib was given in combination with FOLFIRI and bevacizumab in successive cohorts of 3 patients, at doses of 12 mg/m2, 15 mg/m2, 18 mg/m2 on days 1 through 5 of two 14-day cycles. Primary end points of the trial included objective response rate (ORR) in patients who received at least 1 cycle of treatment, while secondary end points included PFS and reduction in KRAS allelic burden assessed by liquid biopsy.

Six patients were treated at dose level 0 (onvansertib 12 mg/m2), 3 patients were treated at dose level +1 (onvansertib 15 mg/m2) and 6 patients were treated at dose level +2 (onvansertib 18 mg/m2). Of these patients, 2 remain on treatment at dose level +2 and 1 patient remains on treatment at dose level 0.

The median age of patients included on the study was 60 years, and 53% (n = 8) of them were male. Of the patients who participated in the study, 53% (n = 8) had an ECOG performance status of 1, 20% (n = 3) presented with liver-only metastasis and 40% presented with liver and other metastases. Sixty percent of patients (n = 9) presented with more than 2 metastatic organs, and 67% (n = 10) had received prior bevacizumab.

Additional results from the study showed that 10 patients had a KRAS variant detected by digital droplet PCR at baseline, and clinical responses were observed across different KRAS variants, including the 3 most commonly observed in CRC. The greatest decreases in KRAS mutant allelic frequency (MAF) after 1 cycle of treatment were observed in patients who achieved a PR (range, -78% to -100%). Patients with PR and stable disease tended to have lower on-treatment KRAS MAF than those who had early progressive disease.

The most common treatment-emergent adverse effects (AEs) experienced with the combination included neutropenia (n= 11), fatigue (n = 11) and nausea (n = 9); most of these effects were grade 1 and 2 in severity, although neutropenia had the highest instance of AEs that were grade 3 or higher (n = 4, grade 3; n = 4, grade 4).

Four patients had dose-limiting toxicities (DLTs) attributed to the 5-FU bolus. One patient who received onvansertib at the dose level of 12mg/m2 experienced grade 4 neutropenic fever, while 3 patients who received the agent at the dose level of 18 mg/m2 reported grade 4 neutropenia.

Currently, 3 additional patients are being enrolled to receive onvansertib at a dose level of 15 mg/m2 to further explore the safety of the agent at that dose level. Overall, only 9% of all AEs reported were grade 3 or 4, and no major unexpected toxicities were determined to be associated with onvansertib. Grade 3 or 4 toxicities were managed by dose delay, growth factor support, or discontinuation of the 5-FU bolus. Notably, no patients went off trial because of neutropenia.

The phase 2 portion of the study will further examine the safety and efficacy of onvansertib in combination with FOLFIRI and bevacizumab. Investigators will also evaluate the value of KRAS assessment through liquid biopsy to predict treatment response.

Ahn DH, Ridinger M, Erlander E, et al. A phase Ib/II study of the polo-like kinase 1 (PLK1) inhibitor, onvansertib, in combination with FOLFIRI and bevacizumab for second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC). 

January 27, 2021 - The combination of the polo-like kinase 1 inhibitor, onvansertib, with FOLFIRI and bevacizumab was found to have preliminary activity and favorable tolerability when used as a second-line treatment for patients with KRAS-mutated metastatic colorectal cancer.

Onvansertib Plus FOLFIRI/Bevacizumab Shows Preliminary Efficacy, Tolerability in Second-Line mCRC 

A shorter course of stereotactic body radiotherapy (SBRT) has been shown to have encouraging efficacy with favorable toxicity when used in patients with high-risk prostate cancer in a multi-institutional, international setting, according to findings from a study published in the 

International Journal of Radiation Oncology, Biology, Physics

Led by investigators at the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center, the study found that SBRT, which delivers higher doses of radiation therapy over the course of 5 or fewer treatments, is safe and as effective as the standard 45-day course of radiation therapy in this patient population.

 However, further prospective studies are needed to determine the optimal dose and target volume of SBRT in these patients.

“These findings suggest that SBRT, which condenses radiation treatment for prostate cancer into as few as 4-5 sessions (as compared with 20-45 sessions previously), is safe and effective in a broad setting for patients with high-risk prostate cancer,” lead study author Amar U. Kishan, MD, an assistant professor of radiation oncology at the David Geffen School of Medicine at UCLA and researcher at the UCLA Jonsson Comprehensive Cancer Center, told OncLive. “This has previously been shown in patients with low- and intermediate-risk prostate cancer but extending these findings to [those with] high-risk prostate cancer broadens applicability [of this approach].”

SBRT can be considered for patients with high-risk prostate cancer, as long as they have social or medical hardships that prevent longer courses of radiation therapy, according to 2020 National Comprehensive Cancer Network guidelines. However, guidelines issued by the European Association of Urology are less supportive of this. 

The latter note that the major evidence to support ultra-hypofractionation for this patient population is based on data yielded from a subset of 126 patients who were enrolled to the randomized phase 3 HYPO-RT-PC trial (ISRCTN45905321). Participants did not receive concurrent androgen deprivation therapy (ADT), which is now considered a standard of care for patients with high-risk disease receiving definitive radiotherapy. The authors of that trial concluded that their general conclusions of oncologic equivalency may not be applicable to patients with high-risk prostate cancer. Other published prospective data supporting SBRT for this patient population are limited.

Earlier research led by investigators at UCLA provided significant evidence that a shortened regimen of radiation therapy could be a feasible treatment option for patients with low- and intermediate-risk prostate cancer.

 Investigators decided to broaden this study to see whether a shorter treatment course of radiation could be used in patients with more aggressive disease.

For this research, investigators collected patient-level data from 7 institutions with phase 2 studies and prospective databases. Data were pooled for a total of 344 patients with a minimum follow-up of 24 months. Biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) were estimated using a Kaplan-Meier framework, while Fine and Gray competing risk and Cox proportional hazards regression models were created to evaluate the association between time to biochemical recurrence (BCR) and time to distant metastasis and prespecified variables of interest. Logistic regression models were developed to evaluate associations between acute and late grade 2 or higher genitourinary and gastrointestinal and a priori determined variables, like age, dose per fraction, ADT use, and nodal radiotherapy.

The median follow-up on the study was 49.5 months (range, 35.8-61.9). Seventy-two percent of patients (n = 248) received ADT, with a median duration of 9 months. Results showed that the estimated BCRFS and DMFS rates at 4 years were 81.7% (95% CI, 77.2%-86.5%) and 89.1% (95% CI, 85.3%-93.1%), respectively. Seventeen percent of patients (n = 59) had a BCR and 8% (n = 26) experienced distant metastases.

Multivariable competing risk analyses revealed that 7 Grey (Gy) per fraction versus 8 Gy per fraction was significantly linked with increased risk of BCR (subdistribution HR [sHR], 2.15; 95% CI, 1.07-4.32; 

 = .03), as was natural log initial prostate-specific antigen (sHR, 1.42; 95% CI, 1.0-1.08; 

 = .02). Additionally, investigators did not observe any significant predictors of time to distant metastases.

Cause-specific models showed comparable results with regard to BCR and distant metastases. Here, a 1-year increase in age at treatment was found to be significantly linked with increased BCR risk (HR, 1.04; 95% CI, 1-1.07; 

BCRFS was found to be significantly greater in the patients who received ADT (log-rank 

 = .009), although no significant difference was observed with DMFS (log-rank 

 = .097). The cumulative incidence of BCR was observed to be substantially lower in the patients who received ADT (

 value, .017 per Gray’s test), while the cumulative incidence of distant metastases was not different (

Regarding safety, acute grade 2 or greater genitourinary (GU) toxicity was reported in 18% of patients, while 5% of patients experienced gastrointestinal (GI) effects. No acute grade 3 or higher GU or GI effects were observed. Notably, a dose per fraction of 7 Gy was linked with lower odds of acute grade 2 or higher GU toxicity, while a dose per fraction of 8 Gy was associated with higher odds of this toxicity (odds ratio [OR], 0.09; 95% CI, 0.02-0.48; 

The 4-year cumulative incidence estimate for late grade 2 or higher GU toxicity was 17.6% (95% CI, 13.6%-21.9%), while this estimate was 6.4% (95% CI, 3.7%-10.1%) for GI toxicity.

Moreover, the crude incidences of late grade 3 or higher GU toxicity was 2.3% versus 0.9% for GI toxicity, with a median time to onset of 21 months and 22 months, respectively.

Although the results of this study highlight the efficacy of this approach, and overall toxicity rates were low and consistent with prior data with SBRT in patients with low- and intermediate-risk disease, the study still had limitations. For one, this analysis focused on multiple single- arm phase 2 studies and prospective registries. Due to the non-randomized nature of the study, this research cannot provide level I evidence to support SBRT for use in this patient population. 

The ongoing randomized PACE-C trial is expected to provide additional level 1 evidence concerning the efficacy of SBRT vs conventional radiotherapy among patients with HRPCa.

“There are several intriguing avenues [for future exploration]. First and foremost, large randomized trials, such as PACE-C run out of the United Kingdom, will be critical to cement SBRT as the standard option, as opposed to a standard option, so we eagerly await that,” Kishan told OncLive. “Second, multiple ongoing studies are [being done] to find out how we can best optimize treatment in patients with more aggressive features, perhaps by adding drugs or selectively increasing the dose, and de-escalating treatments in patients with less aggressive features. Third, technological advances, such as direct magnetic resonance imaging–guided radiotherapy, may help us improve the precision of this treatment further and [this is] being actively studied.”

van Dams R, Jiang NY, Fuller, DB, et al. Stereotactic body radiotherapy for high-risk localized CARcinoma of the prostate (SHARP) consortium: analysis of 344 prospectively treated patients. 

. Published online January 22, 2021. doi:10.1016/j.ijrobp.2021.01.016

Study finds shorter radiation regimen safe, effective for men with advanced prostate cancer. News release. UCLA Health. January 25, 2021. Accessed January 26, 2021. 

January 27, 2021 — A shorter course of stereotactic body radiotherapy has been shown to have encouraging efficacy with favorable toxicity when used in patients with high-risk prostate cancer in a multi-institutional, international setting. 

Shorter Course of SBRT Proves Safe, Effective in High-Risk Prostate Cancer 

Patients with colorectal cancer (CRC) who had molecular residual disease (MRD) positivity immediately after surgery were found to have a high risk of disease recurrence and longitudinal monitoring increased the predictive power of circulating tumor DNA (ctDNA), according to data from a study presented during the virtual 2021 Gastrointestinal Cancers Symposium.

Moreover, molecular recurrence was detected using ctDNA a median of 8 months prior to radiological detection of recurrence. Longitudinal testing with ctDNA also outperformed carcinoembryonic antigen (CEA) testing in the prediction of recurrence-free survival (RFS). 

“To get ctDNA implemented in the clinic, we first have to test it in specific clinical settings using randomized trials. One such trial could be an escalation trial for the [patients with] stage I and low-risk stage II [disease],” lead study author Tenna Vesterman Henriksen, PhD, of Aarhus University, said in an oral presentation of the research. “Currently, these patients do not receive any adjuvant chemotherapy after surgery, but 10% to 15% of them may be undertreated, so they go on to have disease recurrences. These patients could potentially benefit from adjuvant chemotherapy.”

The motivation for this study was inspired by the high relapse rates reported in patients with CRC (range 20%-30%), despite curative intent treatment. Identifying MRD in patients could allow for better recurrent risk assessment, and earlier detection of recurrence could increase the proportion of patients who are treated with curative intent following recurrence, thereby improving survival in this population.

“We believe that ctDNA is a promising marker for MRD detection, and that's the marker that we've been using in this study,” Henriksen noted.

The main objective of the study was to use ctDNA to detect MRD and arrange patients into subgroups of those with high risk and low risk of recurrence. Investigators also set out to evaluate the post-therapy risk of relapse in patients with ctDNA positivity and to identify the lead time for ctDNA detection compared with recurrence on computerized tomography (CT) scans.

To do this, investigators recruited patients from surgical centers in Denmark and Spain and collected tumor tissue samples. Blood samples were also collected before and directly after surgery. In some patients with CRC, blood samples were collected every 3 months after surgery for up to 3 years. Patients were monitored by CT scans at 12 months and 36 months after surgery. The CT scans formed the clinical basis for which the ctDNA data from blood samples were compared.

The cohort for this study was comprised of a total of 260 patients with stage 1 (n = 4), stage 2 (n = 90), and stage 3 (n = 166) CRC. Of those patients, 48 had relapsed. The median follow-up for patients who did not relapse was 29.9 months (range, 1.2-51.0). Some patients in the cohort were treated with adjuvant chemotherapy, the majority of which had stage 2 and stage 3 disease.

The detection technique used for ctDNA was the Signatera approach, a tumor-informed strategy in which the tumor and peripheral blood cells of the patient are exome sequenced to identify patient- and tumor-specific mutations. Investigators then picked out 16 clonal mutations that they used to design the Signatera ctDNA assay, which was then used against the plasma samples to monitor the level of ctDNA before and at several time points after surgery. 

The first time point at which the ctDNA was examined was directly after surgery. These blood samples were drawn within 2 months following surgery and before the start of neoadjuvant chemotherapy. Investigators were able to stratify patients into 2 groups: those who were ctDNA negative (n = 198) and those who were ctDNA positive (n = 20). When looking at recurrent rates, a very low recurrence rate was observed amongst the ctDNA-negative group, at 13%, compared with a higher recurrence rate in the ctDNA-positive group, at 80%. However, not all patients with ctDNA positivity experienced disease recurrence.

“We were wondering about this until we looked into the fact that 19 out of the 20 ctDNA-positive patients received adjuvant chemotherapy after their blood samples were drawn, Henriksen said. “In fact, the 4 patients who did not experience the disease recurrence but were ctDNA positive, so 20%, all received adjuvant chemotherapy.”

This indicated that the outcome was modified by adjuvant chemotherapy, according to Henriksen; it also suggested that those patients were likely cured of residual disease following surgery by receiving adjuvant chemotherapy.

“Hopefully, this could indicate that there is a benefit for ctDNA-positive patients to, in some cases, receive adjuvant chemotherapy,” Henriksen added. 

Beyond stratifying patients into groups with high and low risk of recurrence directly after surgery, investigators also examined that data after end of treatment. When looking at a blood sample drawn after treatment with adjuvant chemotherapy, investigators found a low recurrence rate in the ctDNA-negative group, at 12.5%, and an even higher recurrence rate than they had seen before in the ctDNA-positive group, at 83.3%.

With the inclusion of longitudinal sampling, drawn every 3 months after surgery, the recurrence rate in the ctDNA-negative group dropped to 3.4%, which indicates that serial sampling has a benefit over just single time point sampling. Using serial sampling, investigators evaluated the lead time achieved by using ctDNA (n = 29) compared with clinical CT scans (n = 29).

The result was a positive lead time in most cases, and ctDNA had a median lead time of 8.1 months compared with the CT scans.

Lastly, investigators compared ctDNA with CEA, an already established biomarker. To do this, CEA measurements were done at the same time points as the ctDNA, and the single time point measurements of CEA post surgery (n = 175; hazard ratio [HR], 1.3; 95% CI, 0.56-0.32; 

 = .524) and post adjuvant chemotherapy (n = 99; HR, 1.4; 95% CI, 0.44-4.2; 

 = .596) did not have any predictive power for RFS, although longitudinal samples did show some predictive power (n = 197; HR, 4.9; 95% CI, 3.2-15; 

 <.0001). However, when compared with ctDNA (n = 197; HR, 95.7; 95% CI, 28-322; 

When compared in a multivariable analysis, the predictive power of the ctDNA samples was much greater than CEA, with hazard ratios of 80.55 (95% CI, 23.1-281) versus 1.8 (95% CI, 0.77-4.0), respectively.

“This indicates that ctDNA is a stronger biomarker compared with CEA in terms of RFS,” concluded Henriksen.

Henriksen TV, Tarazona N, Reinert T, et al. Circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, and early relapse detection after treatment in colorectal cancer patients. 

January 26, 2021 — Patients with colorectal cancer who had molecular residual disease positivity immediately after surgery were found to have a high risk of disease recurrence and longitudinal monitoring increased the predictive power of circulating tumor DNA. 

Postoperative MRD Positivity Linked With Reduced RFS in CRC 

All patients with active cancer, or with active, recent, or planned cancer treatment, should be considered highest priority to receive one of the coronavirus disease 2019 (COVID-19) vaccines that have been granted emergency use authorization from the FDA, according to guidance released by the National Comprehensive Cancer Network (NCCN).

The NCCN’s COVID-19 Vaccine Committee, which is comprised of hematology and oncology experts who specialize in infectious diseases, vaccine development and delivery, medical ethics, and health information technology, released these recommendations to assist cancer care providers in making more informed decisions to better protect their patients from the virus. The recommendations decided upon were based on all available evidence and expert consensus.

Among the network’s top recommendations are:

Patients with cancer should be prioritized for vaccination, as they are CDC priority group 1b or 1c, and they should be immunized once the vaccine is available.

Immunization is recommended for all patients on active therapy, with the understanding that limited safety and efficacy data are available.

Reasons for delay of vaccines in this population are comparable to the general public, such as recent exposure to the virus, as well as other cancer-specific factors. Immunization should be delayed for at least 3 months after hematopoietic cell transplantation (HCT) or engineered cellular therapy, such as CAR-T cell therapy, to maximize the effectiveness of the vaccine.

All caregivers and household contacts of patients with cancer should also be vaccinated when the option is available to them.

“One of our primary goals is reducing morbidity and mortality,” Sirisha Narayana, MD, associate professor of medicine and chair of the UCSF Ethics Committee at University of California San Francisco Health, stated in a press release. “We also have to take social determinants of health into account and make special efforts for people in high-risk communities.”

In the event of limited vaccine supply, the NCCN specified in their guidance that patients with active cancer on treatment, including those on hematopoietic and cellular therapy; those planning to begin treatment; and those who received treatment less than 6 months ago, should be among the first to be immunized. Patients receiving hormonal therapy are the only exception to this.

The guidance also recommended that cancer-care providers consider additional risk factors in patients that could put them at higher risk for COVID-19 infection, such as advanced age, namely those 65 years and older; other comorbidities, such as chronic pulmonary, cardiovascular or renal disease; as well as social and demographic factors, including poverty, limited access to healthcare, and underrepresented minorities.

“Right now, there is urgent need and limited data,” Steve Pergam, MD, MPH, associate professor in the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center; infection prevention director at Seattle Cancer Care Alliance; and co-leader of the NCCN COVID-19 Vaccine Committee, added in the release . “Our number one goal is helping to get the vaccine to as many people as we can. That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID- 19. The evidence we have shows that people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

The guidance from the NCCNalso acknowledges that, although trial data have demonstrated that the COVID-19 vaccine is safe and effective amongst the general population, the efficacy of these vaccines in patients with cancer specifically, is still relatively unknown.

Vaccine trials have shown data indicating a decrease in the incidence of COVID-19 infection and complications, but whether these vaccines fully prevent infection and subsequent transmission is still unclear. As such, it is recommended by the NCCN that patients with cancer, as well as their caregivers and household contacts, continue to wear masks and that they maintain social distancing and follow other COVID-19 preventative measures, even after vaccination.

“The medical community is rising to one of the biggest challenges we have ever faced,” Robert W. Carlson, MD, chief executive officer of the NCCN, added in the release. “The COVID-19 vaccines exemplify the heights of scientific achievement. Now we have to distribute them quickly, equitably, safely and, efficiently, using clearly defined and transparent principles.”

The NCCN COVID-19 Vaccine Committee will continue to meet regularly to refine the recommendations for these and other issues.

NCCN shares new guidance principles for vaccinating people with cancer against COVID-19. News release. National Comprehensive Cancer Network. January 22, 2021. Accessed January 22, 2021. 

https://www.nccn.org/about/news/newsinfo.aspx?NewsID=2552

NCCN. Preliminary recommendations of the NCCN COVID-19 vaccination advisory committee, version 1.0. Accessed January 22, 2021. 

https://www.nccn.org/covid-19/pdf/COVID-19_Vaccination_Guidance_V1.0.pdf

All patients with active cancer, or with active, recent, or planned cancer treatment, should be considered highest priority to receive one of the coronavirus disease 2019 vaccines that have been granted emergency use authorization from the FDA.

Courtney Marabella

Articles

NeoADAURA Trial Slated to Examine Neoadjuvant Osimertinib in Resectable EGFR+ NSCLC

Onvansertib Plus FOLFIRI/Bevacizumab Shows Preliminary Efficacy, Tolerability in Second-Line mCRC

Shorter Course of SBRT Proves Safe, Effective in High-Risk Prostate Cancer

Postoperative MRD Positivity Linked With Reduced RFS in CRC

NCCN Releases COVID-19 Vaccination Guidance for Patients With Cancer