Patients with resectable, stage II to IV cutaneous squamous cell carcinoma (CSCC) achieved an encouraging rate of pathologic complete response (pCR) following adjuvant cemiplimab (Libtayo) treatment, according to initial findings from a phase 2 trial (NCT04154943) presented at the 2022 ESMO Congress.

In total, 63.3% of patients (95% CI, 51.7%-73.9%) experienced near or complete disappearance of their tumors when treated with the anti–PD-1 monotherapy—representing the highest response rates to this type of therapy in solid tumors, according to a press release issued by The University of Texas MD Anderson Cancer Center (MD Anderson) in Houston.

Neil D. Gross, MD, FACS, professor and director of clinical research in the Department of Head and Neck Surgery at MD Anderson, presented part 1 of the data which were published simultaneously in the 

Investigators observed a pCR in 40 patients (50.6%; 95% CI, 39.1%-62.1%) and a pathological major response (pMR) in 10 patients (12.7%; 95% CI, 6.2%-22.0%) under independent central pathology review (ICPR). Twenty patients (25.3%) experienced no pCR or pMR, and 9 patients (11.4%) did not undergo pathologist evaluation. Responses were confirmed by ICPR.

Moreover, 54 patients demonstrated an objective response on imaging (68.4%; 95% CI, 56.9%-78.4%), which included 5 patients with complete responses (6.3%), 49 with partial responses (62.0%), 16 with stable disease (20.3%), 8 with progressive disease (PD; 10.1%), and 1 patient with no imaging-based evaluation (1.3%). The disease control rate was 89% (95% CI, 80%-95%).

Adverse events (AEs) of any grade occurred in 69 patients (87.3%), with 14 patients (17.7%) experiencing grade 3 or higher events. The most common AEs of any grade were fatigue (30.4%), as well as diarrhea, nausea, and maculopapular rash (13.9% each).

Treatment-related AEs (TRAEs) occurred in 57 patients (72%), with the most common being fatigue (28%), maculopapular rash (14%), and diarrhea (11%). Twelve patients (15%) experienced immune-related AEs, including 3 patients (4%) with grade 3 immune-related AEs.

Four patients died; however, only 1 death (exacerbation of cardiac failure) was considered treatment related.

Investigators also examined the correlation between treatment response with tumor mutation burden and PD-L1 expression.

“There was a higher mutation burden among patients who had a pMR or pCR, and there was significant overlap between these 2 groups, indicating that this, at least in this cohort, was not useful in segregating patients who respond to treatment,” Gross said.

However, when evaluating PD-L1 expression, there were responders in those with PD-L1 expression below 1% (n = 15) as well as at 1% or above (n = 41). “There were 3 patients who were PD-L1 negative, but they still had a complete pathologic response,” he explained. “About a third of patients who are PD-L1 negative have a deep pathologic response, suggesting that this biomarker alone may be insufficient for segregating patients for treatment. This underscores the need for histologic confirmation of response. Still, hopefully, we’ll have biomarkers in the future that can help better direct us,” Gross concluded.

In the confirmatory, international, multicenter, nonrandomized, phase 2 study, patients received 350 mg cemiplimab every 3 weeks for up to 4 doses followed by imaging after 2 doses before undergoing surgery with curative intent (n = 79) in part 1 of the study. In part 2 of the study—for which follow-up is ongoing—patients received radiotherapy at the investigator’s discretion.

pCR (0% viable tumor) per ICPR served as the primary end point. Secondary end points included a pMR (<10% viable tumor) per IPCR, pCR and pMR per investigator pathology review, radiological objective response rate per RECIST v1.1, safety, and tolerability.

Median patient age was 73 years (range, 24-93). The majority of patients were male (84.8%), White (87.3%), presented with a primary tumor in the head and neck (91.1%), had ECOG performance of 0 (75.9%), and had stage III disease (48.1%).

In total, 62 patients received all 4 doses, and 70 patients underwent surgery. Of the 9 who did not undergo surgery, 3 declined because imaging showed their cancer responded to the immunotherapy and 2 experienced PD. The rest were either lost to follow-up, died, or were not compliant.

Christian U. Blank, MD, PhD, from the Department of Medical Oncology in the Division of Molecular Oncology and Immunology at The Netherlands Cancer Institute, and a discussant of the presentation, noted that the research leaves remaining questions. “For me, the take home message is that we have very early data, only pathologic response at the moment, but also very promising data,” he said. “Maturation is needed to learn whether CSCC [pathologic response] rate is a surrogate marker for event-free survival. Then, do we really need 4 doses of cemiplimab? Can we also achieve the same result with 2 doses? I hope we will see, as soon as possible, a randomized trial to establish this therapy approach in cutaneous squamous cell carcinoma.”

Gross N, Miller DM, Khushanlani N, et al. Neoadjuvant cemiplimab in patients (pts) with stage II–IV (M0) cutaneous squamous cell carcinoma (CSCC): Primary analysis of a phase II study. 

. 2022;33(suppl 7):789O. doi:10.1016/annonc/annonc1059

Immunotherapy before surgery induces complete response in more than half of patients with common skin cancer in international study. News Release. Published September 12, 2022. Accessed September 12, 2022. https://bit.ly/3d16OgB

Gross N, Miller DM, Khushanlani N, et al. Neoadjuvant cemiplimab for stage II to IV cutaneous squamous-cell carcinoma. 

Articles

Neoadjuvant cemiplimab elicited promising pathologic complete responses in patients with cutaneous squamous cell carcinoma. 

Promising Pathologic Complete Response Rate Observed With Neoadjuvant Cemiplimab in Cutaneous Squamous Cell Carcinoma

A 7-year follow-up of the phase 3 SOLO1/GOG-3004 trial (NCT01844986) showed that maintenance therapy with olaparib (Lynparza) reduced the risk of death in women with newly diagnosed, advanced, 

-positive ovarian cancer by 45% and no new safety signals, according to a presentation at the European Society for Medical Oncology Congress 2022. 

As of the data cutoff of March 7, 2022, median overall survival (OS) was not reached with olaparib treatment, compared with 75.2 months with placebo treatment (HR, 0.55; 95% CI, 0.40-0.76; 

 = .0004). The 7-year OS rates were 67.0% in the olaparib arm and 46.5% in the placebo arm. The median duration of follow-up in the olaparib and placebo arms were 88.9 months (range, 85.7-93.6) and 87.4 months (range, 84.3-91.7), respectively.

“These results support the use of maintenance olaparib to achieve long-term remission in women with newly diagnosed advanced ovarian cancer and a 

 mutation. The potential for cure may also be enhanced,” Paul A. DiSilvestro, MD, director of the Program in Women’s Oncology for Women & Infants Hospital of Rhode Island and Care New England Health System, and division director of gynecologic oncology in the Department of Obstetrics and Gynecology at The Warren Alpert Medical School of Brown University, said during a presentation of the data, which were simultaneously published in the 

In total, 45.3% of patients in the olaparib arm and 20.6% in the placebo arm had still not received a first subsequent treatment, while 44.3% of patients given placebo received a PARP inhibitor in a subsequent line of therapy, compared with 14.6% of patients in the olaparib group.

“The OS benefit was seen despite over 40% of patients in the placebo group receiving subsequent PARP inhibitor therapy,” DiSilvestro said.

The time to first subsequent therapy or death (TFST) was also substantially delayed with olaparib, compared with placebo (median, 64.0 months vs 15.1 months; HR 0.37; 95% CI, 0.28-0.48), and this benefit extended beyond first subsequent therapy into the time to second subsequent therapy or death (TSST) (93.2 months vs 40.7 months; HR 0.50; 95% CI, 0.37-0.67).

“These 7-year results provide further confirmation that the benefit of maintenance olaparib extends well beyond its 2-year treatment cap,” DiSilvestro added.

The incidence of MDS/AML remained low in the olaparib and placebo arms (1.5% vs 0.8%, respectively) and new primary malignancies remained balanced between arms (5.4% vs 6.2%). Pneumonitis occurred in 5 patients treated with olaparib.

The most frequent adverse events in the olaparib and placebo groups included nausea (77.7% vs 37.7%, respectively), fatigue/asthenia (64.2% vs 41.5%), vomiting (40.0% vs 14.6%), anemia (40.0% vs 10.0%), diarrhea 34.6% vs 24.6%), arthralgia (28.8% vs 30.0%), constipation (27.7% vs 19.2%), abdominal pain (25.8% vs 19.2%), headache (23.1% vs 23.8%), neutropenia (23.1% vs 11.5%), dysgeusia (21.5% vs 3.8%), dizziness (20.4% vs 15.4%), decreased appetite (20.4% vs 10.0%), and cough (16.9% vs 21.5%).

“Ten-year survival in women with newly diagnosed advanced epithelial ovarian cancer is 17%. Relapsed advanced ovarian cancer is typically incurable, highlighting the need for effective first-line therapies that delay relapse, prolong survival, and enhance the potential for cure,” DiSilvestro explained. “We reported a descriptive analysis of OS after 7 years of follow-up in SOLO1, a clinically relevant timepoint for survivorship, and the longest follow-up for any PARP inhibitor in newly diagnosed advanced ovarian cancer

In the randomized, double-blind, placebo-controlled, phase 3 trial, which was conducted across 15 countries, patients were randomly assigned 2:1 to receive either 300 mg of olaparib twice daily (n = 260) or placebo (n = 131) orally as maintenance monotherapy for up to 2 years or until disease progression.

Investigator-assessed PFS served as the primary end point. Secondary end points included OS, TFST, TSST, and safety.

To be eligible for enrollment, patients had to be 18 years or older; have newly diagnosed, FIGO stage III to IV, high-grade serous or endometrioid ovarian, primary peritoneal or fallopian tube cancer; a 

 mutation; ECOG performance status of 0 or 1; cytoreductive surgery; and clinical complete or partial responses after platinum-based chemotherapy.

In the olaparib arm, the majority of patients had stage III disease (84.6%) and a 

mutation (73.5%). In total, 61.9% of patients underwent upfront surgery, while 36.2% had interval cytoreductive surgery, of which 81.9% of patients reported with a clinical complete response.

Initial findings, presented in 2018, showed that after a median follow-up of 41 months, the risk for disease progression or death was 70% lower with olaparib, compared with placebo (HR, 0.30; 95% CI, 0.23-0.41; 

 < .001), with a median PFS not reached with olaparib vs 13.8 months with placebo. The 3-year PFS rates were 60.4% and 26.9%, respectively.

In 2021, investigators reported an updated, post-hoc analysis of PFS from the trial, after 5 years of follow-up. The data cutoff for this updated, post-hoc analysis was March 5, 2020. In the 5-year post-hoc analysis, median PFS was 56.0 months (95% CI, 41.9-not reached) with olaparib, compared with 13.8 months (95% CI, 11.1-18.2) with placebo (HR, 0.33; 95% CI, 0.25-0.43). Moreover, 48.3% of patients in the olaparib group vs 20.5% of patients in the placebo group were progression free at 5 years.4

DiSilvestro P, Banerjee S, Colombo N, et al. Overall survival (OS) at 7-year (y) follow-up (f/u) in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) who received maintenance olaparib in the SOLO1/GOG-3004 trial. 

. 2022;33(S7):(S779). doi:10.1016/j.annonc.2022.07.645

DiSilvestro P, Banerjee S, Colombo N, et al. Overall survival with maintenance olaparib at a 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: the SOLO1/GOG 3004 trial. 

Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. 

. 2018;379:2495-2505. doi:10.1056/NEJMoa1810858

4. Banerjee S, Moore K, Colombo N, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. 

. 2021; 22(12): P1721-1731. doi:10.1016/S1470-2045(21)00531-3

Women with ovarian cancer who received 2 years of maintenance therapy with olaparib experienced a 45% reduction in risk of death, according to a 7-year follow-up. 

Olaparib Maintenance Yields Long-Term Remission for Women With BRCA+ Ovarian Cancer

The implementation of a verification process for the distribution of investigational agents to patients to take orally on their own has proven efficacious at Smilow Cancer Hospital, according to a presentation at the 47th Annual Oncology Nursing Society (ONS) Congress.

“Independent verification of documentation is paramount to patient safety. With high-risk medications, verification administration and documentation of oral investigational chemotherapy and immunotherapy agents had not been in alignment with our policy,” Jeramy Tabuzo BSN, RN, OCN, clinical trials oncology nurse, Smilow Cancer Hospital, Yale New Haven Health in Connecticut, said during her presentation at the Congress.

“Pulling together an interdisciplinary team has created a new process that we developed and implemented to ensure patient safety and practice according to our institutional standards.”

At Smilow, a National Cancer Institute (NCI)-designated Comprehensive Cancer Center, Tabuzo and colleagues administer oral investigational chemotherapy drugs as part of their ongoing phase 1 trials. Through the administration process, patients receive their drug bottle on day 1 of the study, and are responsible for taking the agent at specific time points thereafter.

Their phase 1 clinical trial infusion unit is comprised of 12 infusion chairs, where they see 12 to 20 patients per day, across 142 active trials. Among these trials, there are approximately 64 oral investigational trials.

“In 2018, our nursing policy on chemotherapy verification was revised and required nurses to practice independent verification at the bedside, or chairside,” explained Tabuzo. “However, the infrastructure of our electronic medication administration record does not support our practice and policy.”

For example, she added, the oral drug released to the patient is not on electronic Medication Administration Record (eMAR) and has not allowed for barcode scanning at the time of disbursement and administration.

Therefore, Tabuzo and her colleague aimed to safely administer oral investigational chemotherapy and immunotherapy agents in accordance with current nursing policies; in particular, through completing dual independent nurse verification and appropriately scanning and documenting oral drug administration.

To do so, they had a committee of 6 individuals, comprised of the EPIC/Beacon coordinator, a pharmacy application IT specialist, an oncology pharmacist, an investigational drug services manager, a nursing professional development specialist, and an infusion nurse. The committee identified components that needed to be changed for new processes to improve workflow and dispense and administer oral medications that allow for independent 2-nurse verification through barcode scanning.

In turn, once these processes were developed, the committee educated and dispersed the new processes to nurses, pharmacists, and physicians. Lastly, the process was then implemented across the Smilow ambulatory units and 15 infusion care centers.

Ordering for oral investigational medication in the treatment plan.

Once released, transferring the order to eMAR.

The pharmacy creating a process to generate the barcode label for scanning the oral investigational drug bottle.

At the chairside, 2-nurse verification process occurring.

If there are no discrepancies, nurse 2 signing off MAR, and nurse 1 proceeding to dispense the drug bottle.

The patient self-administering from the bottle dispensed on day 1 of treatment.

Documenting the patient self-administered the agent, using the smart phrase, “.oralinvestigational” in the nurse’s note.

“Smart phrase is a function in EPIC that we utilize to create the standardized text that can be inserted into the nurse’s notes,” explained Tabuzo. “In our case, if you type in ‘.oralinvestigational’ that will populate the notes with the treatment cycle, the HIC number, the drug name, the dose, and the time that the patient took the medication. The standard documentation supports consistency and efficiency for research data collection.”

Compliance to the new workflow was evaluated by monitoring the number of safety events reported through the electronic event reporting system at Smilow. The system evaluated incorrect bottles dispensed, incorrect doses, and incorrect medication labels. Moreover, barcode scanning compliance was audited using an automated report.

“We also saw direct feedback from nurses, pharmacists, physicians, and clinical trials office staff. To date, nursing has been [satisfied] with [the] policy and no safety events have been reported,” Tabuzo said.

Tabuzo J, Mancini KA. Oral Investigational Chemotherapy/Immunotherapy Verification Process. Presented at: 47th Annual ONS Congress; April 27 – May 1; Anaheim, California. Presentation O26.

Independent verification of documentation is paramount to patient safety.

Independent 2-Nurse Verification Process in Distribution of Oral Investigational Chemo/Immunotherapy Proves Helpful

A post-hoc analysis of the phase 3 REFLECT trial (NCT01781266) indicated that patients with unresectable hepatocellular carcinoma (uHCC) with Child-Pugh class B (CP-B) liver function fared similarly to their Child-Pugh class A (CP-A) counterparts who received lenvatinib (Lenvima). The tumor size reduction was similar between the 2 groups, according to an analysis presentated at the 2021 European Society for Medical Oncology World Congress on Gastrointestinal Cancer.

“The results of this post hoc analysis suggest that patients with uHCC whose liver function deteriorates to CP-B after initiation of therapy may continue to receive lenvatinib,” the researchers wrote.

Results from the randomized, multicenter phase 3 REFLECT study– which led to the FDA’s approval of the agent for the first-line treatment of patients with uHCC – showed a benefit from lenvatinib, compared with sorafenib (Nexavar), irrespective of baseline liver function, including albumin-bilirubin (ALBI) grade 1 or 2 and CP score of 5 or 6.

However, of note, the trial enrolled patients with CP-A liver function per the study inclusion criteria, but not CP-B specifically.

“In the absence of any initial enrollment of patients with CP-B liver function, we conducted a post hoc exploratory analysis of key efficacy and safety outcomes in patients from REFLECT whose liver function had deteriorated to CP-B versus those whose liver function remained CP-A within 8 weeks post-randomization.”

The post hoc analysis assessed overall response rate (ORR), and landmark analyses that began after week 8, including progression-free (PFS) and overall survival (OS), both in patients whose liver function had deteriorated to CP-B and in patients whose liver function remained CP-A within 8 weeks post-randomization. In addition, safety was evaluated from baseline and adjusted by treatment duration.

Among patients treated with lenvatinib in the CP-B (n = 60) and CP-A (n = 413) subgroups, the median percent changes in tumor size from baseline to week 8 were –16.2% (range, –100 to 25) and –15.9% (range, –100 to 187), respectively, compared with 1.7% (range, –36 to 64) and 0% (range, –100 to 106) in patients treated with sorafenib in the CP-B (n = 47) and CP-A (n = 427) subgroups.

In the lenvatinib group, the CP-B and CP-A subgroups demonstrated ORRs of 28.3% (95% CI, 16.9-39.7) and 42.9% (95% CI, 38.1-47.6), respectively. In particular, for the CP-B subgroup of the lenvatinib arm, there were 0 complete responses (CRs), 17 (28.3%) partial responses (PRs), 17 (28.3%) patients with stable disease (SD), 12 (20.0%) with progressive disease (PD), and 14 (23.3%) were not evaluable (NE), compared with 10 (2.4%) CRs, 167 (40.4%) PRs, 142 (34.4%) with SD, 67 (16.2%) with SD, and 27 (6.5%) NE for the CP-A subgroup.

In the sorafenib group, the CP-B and CP-A subgroups demonstrated ORRs of 8.5% (95% CI, 0.5-16.5) and 12.9% (95% CI, 9.7-16.1), respectively. In particular, for the CP-B subgroup of the sorafenib arm, there were 0 CRs, 4 (8.5%) PRs, 12 (25.5%) with SD, 23 (48.9%) with PD, and 8 (17.0%) NE, compared with 4 (0.9%) CRs, 51 (11.9%) PRs, 207 (48.5%) with SD, 129 (30.2%) with PD, and 36 (8.4%) NE.

After week 8, median OS was 6.8 months (95% CI, 2.6-10.3) and median PFS was 3.7 months (95% CI, 1.8-7.4) in lenvatinib-treated patients within the CP-B subgroup, compared with 13.3 months (95% CI, 11.6–16.1) and 6.5 months (95% CI, 5.6–7.4), respectively, in the CP-A subgroup. In the sorafenib-treated CP-B subgroup, median OS and PFS were 4.5 months (95% CI, 2.9–6.1) and 0.5 months (95% CI, 0.1–3.6), respectively, compared with 12.0 months (95% CI, 10.2–14.0) and 3.6 months (95% CI, 0.1–3.6) in the CP-A subgroup.

In the CP-B and CP-A subgroups treated with lenvatinib, the median duration of treatment was 3.2 months (range, 0.3-31.5) and 6.9 months (range, 0.0-35.0), respectively, compared with 1.9 months (range, 1.9 months (range, 0.2-22.4) and 3.7 months (range, 0.1—38.7) in the sorafenib-treated CP-B and CP-A subgroups.

The mean dose intensity of lenvatinib was 8.4 mg/day/patient (standard deviation [SD], 3.07) and 9.5 mg/day/patient (SD, 6.01) in the CP-B and CP-A subgroups, respectively, whereas the mean dose intensity of sorafenib was 653.2 mg/day/patient (SD, 165.75) and 664.8 mg/day/patient (SD, 174.23) in the CP-B and CP-A subgroups, respectively.

Among the CP-B and CP-A patients, rates for grade 3 or higher treatment-related adverse events (TRAEs) in the lenvatinib arm were 3.65% (n = 95) and 1.41% (n = 419), respectively, and 3.38% (n = 42) and 1.71% (n = 388), respectively, in the sorafenib arm.

In their conclusion, the researchers noted, “As this post hoc analysis is limited by its descriptive nature, the efficacy results cannot be compared between CP–B and CP–A subgroups,” adding that further investigation is warranted.

“Although the treatment landscape for patients with unresectable hepatocellular carcinoma (uHCC) has recently expanded, there remains an unmet need for effective treatment options in patients with Child–Pugh class B (CP-B) liver function. Such patients are rarely included in clinical trials,” the researchers wrote in their poster.

In the trial, patients with uHCC were randomly assigned 1:1 to receive lenvatinib – for which dosage was based bodyweight: 12 mg/day for those weighing ≥ 60 kg; 8 mg/day for those weighing < 60 kg) – or sorafenib 400 mg twice daily in 28-day cycles.

At baseline, patients whose liver function deteriorated to CP-B within 8 weeks in the lenvatinib and sorafenib arms, 73.3% and 61.7%, respectively, had an ALBI score of 2, and 60.0% and 44.7% had a CP score of 6. Similarly, among those whose liver function remained CP-A within 8 weeks in both arms, 73.1% and 75.4%, respectively, had an ALBI score of 1, and 83.5% and 78.5% had a CP score of 5.

In the prior analysis, treatment with lenvatinib demonstrated higher ORR, compared with sorafenib, in patients with a CP score of 5 (OR, 4.88; 95% CI, 3.37-7.08) and in those with a CP score of 6 (OR, 5.25; 95% CI, 2.32-11.85), as well as in patients classified as either ALBI grade 1 (OR, 5.48; 95% CI, 3.70-8.10) or ALBI grade 2 (OR, 5.37; 95% CI, 2.61-11.06).

Huynh J, Thet Cho M, Jae-Hoon Kim E, Ren M, Amaya-Chanaga C, Vogel A. Post hoc analysis in patients with unresectable hepatocellular carcinoma who progressed to Child–Pugh B liver function in the phase 3 REFLECT study of lenvatinib vs sorafenib. 

. 2021;32(suppl 3) doi:10.1016/j.annonc.2021.05.133

This article was originally published on OncLive as 

“Lenvatinib Treatment Can Continue in Unresectable HCC With Child–Pugh Class-B Liver Function”

Researchers observed a similar tumor size reduction between 2 arms of patients with hepatocellular carcinoma who were stratified by their liver function class and treated with lenvatinib.  

Patients with Unresectable Hepatocellular Carcinoma with Moderately Impaired Liver Function May Continue Lenvatinib Therapy  

Adjuvant carboplatin and paclitaxel after standard cisplatin-based chemoradiation did not demonstrate improved overall survival or progression-free survival in patients with locally advanced cervical cancer, according to findings from the phase 3 OUTBACK trial that were presented at the 2021 ASCO Annual Meeting.

“Adjuvant chemotherapy given after standard platinum-based chemoradiation for women with locally advanced cervical cancer did not improve OS or PFS. So, the standard treatment should continue to be pelvic chemoradiation with concurrent weekly cisplatin,” lead study author Linda R. Mileshkin, MD, medical oncologist, Peter McCallum Cancer Centre, Melbourne, Australia, said during a presscast ahead of the meeting.

“Our findings don't support giving adjuvant chemotherapy with carboplatin and paclitaxel after chemoradiation with weekly cisplatin. Further research should focus on adjuvant therapies that might be more tolerable and effective when given after standard therapy,” she added.

In the international, randomized phase 3 OUTBACK trial (NCT01414608), the investigators aimed to determine the survival effects from administering adjuvant chemotherapy after standard chemoradiation, compared with standard chemoradiation alone, in 919 patients with locally advanced cervical cancer recruited from April 2011 to June 2017

In total, investigators randomized patients 1:1 to receive either standard cisplatin-based chemo-radiation followed by adjuvant chemotherapy (n = 463) with 4 cycles of carboplatin and paclitaxel or standard cisplatin-based chemo-radiation (n = 456). Adjuvant chemotherapy was administered in 361 women (78%).

Trial eligibility consisted of locally advanced cervical cancer (FIGO 2008 stage IB1 & node positive, IB2, II, IIIB, or IVA); an ECOG score of 0 to 2; squamous cell, adenocarcinoma, or adenosquamous cancer; no nodal disease above L3/4; and disease that was suitable for primary treatment with chemo-radiation with curative intent. Women were stratified by nodal status, participating site, FIGO stage, age, and planned extended-field radiotherapy.

OS at 5 years served as the primary end point. Secondary endpoints included PFS, adverse events (AEs), and patterns of disease recurrence.

Median follow-up was 60 months (IQR, 45-65).

The adjuvant chemotherapy arm demonstrated similar OS at 5 years, compared with the control arm (72% vs 71%, respectively; P = .8), for an HR of 0.90, (95% CI, 0.70-1.17), as well as similar PFS at 5 years (63% vs 61%; P = .61), for an HR of 0.87 (95% CI, 0.70-1.08).

In addition, patterns of disease recurrence were similar in the two treatment groups.

“Even when we looked at subsets of women with high-risk disease, such as those with node positive involvement, there was no benefit from the intervention,” Mileshkin added.

Within a year of randomization, grade 3 to 5 AEs typically seen with chemotherapy occurred in significantly more patients in the adjuvant chemotherapy arm, compared with the control arm (81% vs 62%, respectively). Lastly, Mileshkin noted that quality of life was worse during adjuvant chemotherapy and for the following 3 to 6 months, but returned to being similar between the groups from 12 months onwards.

Cervical cancer is a major global health problem, according to Mileshkin, with more than half a million women diagnosed with the disease each year, “and more than 3000 women will die of this cancer each year, making it the fourth leading cause of cancer-related death in women. … But most women die from cervical cancer…because of the development of distant metastatic disease.”

Although prior, smaller studies suggested that giving more chemotherapy after chemoradiation could improve survival. “And these findings changed practice in some centers,” Mileshkin explained. “However, the international community felt that there were some flaws in these trials and that it was important to perform a confirmatory trial.”

ASCO president Lori J. Pierce, MD, FASTRO, FASCO, added to the OUTBACK trial’s significance. “As we heard, physicians are currently using adjuvant chemotherapy based upon preliminary data and promise it could work. We clearly see it does not work and need to discontinue that practice,” she said. “This tells us that, as clinical researchers, we need more trials for patients with locally advanced cervical cancer using a different therapeutic approach. And I think it also clearly shows the importance of the outcomes of clinical trials, even if the results are negative. Both positive trials and negative trials clearly inform practice.”


Mileshkin LR, MooreKN, Barnes E, et al. Adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: The randomized phase 3 OUTBACK Trial (ANZGOG 0902, RTOG 1174, NRG 0274). Presented at: American Society of Clinical Oncology Annual Meeting; June 4-8, 2021; Virtual. Abstract LBA3.

This article was originally published on OncLive as, "

Adjuvant Chemotherapy Fails to Improve PFS and OS in Locally Advanced Cervical Cancer.

Adjuvant carboplatin and paclitaxel after standard cisplatin-based chemoradiation did not demonstrate improved overall survival or progression-free survival in patients with locally advanced cervical cancer.

Adjuvant Chemo Does Not Improve Survival in Locally Advanced Cervical Cancer

Implementation of an onboarding reference guide served as a useful resource for advanced practice providers (APPs) in treating patients who are undergoing bone marrow transplantation (BMT), according to a poster presentation at the 46th Annual ONS Congress.

“It is known that bone marrow transplant patients are quite complex and require careful management by their providers. As cancer services continue to expand across organizations, advanced practice providers, or APPs, are playing a central role in patient care,” Tanya Lalani, DNP, NP, AOCNP®, a nurse practitioner at Ochsner Health said during a recording at the meeting. “Organizations are growing rapidly and more and more APPs are being hired.”

With this expansion, for example at Ochsner Health, it has become apparent that a structured orientation is necessary to allow for appropriate training for APPs, Lalani added. As a result, she created an onboarding reference guide, also known as the cheat sheet for new BMT APP hires, for reference during and after their orientation period.

In particular, the guide includes step-by-step information on how to perform daily tasks like admissions, discharges, and graft versus host disease documentation. In addition, it includes important phone numbers, frequently used order codes, and the process for performing and documenting procedures, as well as common labs and advanced testing guidelines for BMT patients categorized by hematologic malignancy.

In particular, Lalani added that the guide includes a checklist and a shadowing schedule, which allows an APP to know exactly where they need to be at any given.

Lastly, the guide also includes a quiz to help with discussion points during the orientation period.

Since its implementation, the guide is updated frequently to allow for the most up-to-date information, Lalani said.

“This onboarding guide has been very well received by new hires as well as management,” she concluded. “It has been used by leadership when asking the system for new hires. It has inspired other departments within the organization to create a more structured orientation guide as well. It has also been shared with hematology oncology fellows, and there are future plans to share it with internal medicine residents who rotate through the bone marrow transplant service.”

Lalani T, et al. An Onboarding Reference Guide for New Bone Marrow Transplant Advanced Practice Providers. Presented at: 46th Annual ONS Congress; April 20, 2021; virtual.

The “cheat sheet” assisted advanced practice providers using a step-by-step guide that is updated frequently to allow for the most up-to-date information.

Onboarding Reference Guide Aids APPs Treating Patients Receiving Bone Marrow Transplant

Nurses showed a willingness to learn about patients who identify as lesbian, gay, bisexual, and transgender (LGBT); however, they also reported there is a need for such training, according to survey results presented at the Oncology Nursing Society 43rd Annual Congress.

In scientific and health literature, sexual minorities include individuals who identify as lesbian, gay, bisexual, pansexual, asexual, or queer; gender minorities include those who identify as transgender, transman, transwoman, nonbinary, genderfluid, or queer.

“These terms allow us to encompass sexual orientations (in research) without limiting it at any point,” explained Chasity Burrows Walters PhD, RN, director, patient and caregiver engagement at Memorial Sloan Kettering (MSK) Cancer Center in New York, New York. “Sex is not gender. They are very different. This matters a lot to us in health care because when we think about biology we need to think about anatomy, and in oncology care, this matters for screening purposes.”

Population surveys have suggested between 5.2 and 9.5 million US adults identify as LGBT, but barriers to equitable health care are multifactorial, including negative experiences.

While research demonstrates there have been increasing efforts to educate nursing students in this area, other studies have shown that barriers still persist. For example, sexual and gender minorities have barriers to healthcare like discrimination, insurance, and provider/healthcare system insensitivity. Gender minorities also experience distress from discordance between gender and genitalia, lack of evidence for clinical decision making, and limited exposure, Walters said.

In addition, the LGBT population lacks data in the cancer space, despite the fact that there are overlapping risk factors that can lead to anal, breast, cervical, colorectal, endometrial, lung, and prostate cancers in this group. “We don’t have anything to [reference] to learn about the disparities and risks associated with these populations,” she added.

Therefore, Walters and colleagues aimed to understand oncology nurses’ knowledge, beliefs, and skills regarding LGBT patients to establish warranted training needs. They issued an online survey to 1253 health care professional at MSK, including 941 nurses, to evaluate LGBT healthcare knowledge, beliefs, communication behaviors, willingness to treat LGBT patients, behaviors encouraging LGBT disclosure, and perceived importance of LGBT sensitivity training.

The researchers included 7 items on knowledge adapted from published items; 12 items on beliefs adapted from the Sexual Orientation Beliefs Scale and Attitudes Toward Transgendered Individuals Scale, as well as published items; and 18 items on skills that were adapted from the Gay Affirmative Practice Scale, as well as quantitative and qualitative items added by the study team.

Notably, 81 survey participants identified as LGBT, and 810 (86.1%) said they had a friend or family member in the LGBT community.

In total, 86% of nurses surveyed had experience caring for individuals who identified as lesbian, gay, or bisexual, while 31% had experience with those who identified as transgender. However, only 4.7% of nurses were able to answer all knowledge items in the survey correctly, and about half identified 3 of the 7 answers correctly.

Higher knowledge scores appeared to be associated with favorable beliefs about sexual orientation and gender identity, favorable beliefs about LGBT healthcare, more open communication behaviors, greater encouragement regarding LGBT status disclosure, and greater perceived importance of LGBT sensitivity training.

The researchers noted these results are serving the foundation for the development of a communication skills training for nurses, and in the near future they will contribute to a mixed methods study comparing healthcare providers and LGBT patient preferences and perceptions regarding LGBT patient care.

“Across the board, we heard loud and clear from our nursing staff they want more training in this area,” Walters added.

Walters C, Banerjee S, Staley J, Haviland K. Nurses’ knowledge, beliefs, and skills toward LGBT patients. Presented at: Oncology Nursing Society 43rd Annual Congress; May 17-20, 2018; Washington DC. 

https://ons.confex.com/ons/2018/meetingapp.cgi/Paper/3718

A recent survey showed that nurses are willing to be trained in how to offer an affirmative healthcare experience to individuals who identify as lesbian, gay, bisexual, or transgender; however, only 4.7% were able to demonstrate knowledge of this patient community.

Nurses Show Interest in Learning About LGBT Patients With Cancer

Physical activity interventions should be individualized for adolescents and young adults (AYAs) with cancer, according to study findings presented at the Oncology Nursing Society 43

Of note, these interventions are needed during and after treatment, said Jeanne Erickson PhD, RN, University of Wisconsin-Milwaukee College of Nursing.

Despite the fact that cancer is the leading disease-related cause of death in AYAs, this group of individuals tends to be an understudied patient population. As a result, few studies have evaluated physical activity interventions in this population.

In addition, staying physically active has important short- and long-term benefits for patients with cancer, including reduced symptom severity, improved physical function, and better tolerance to treatment. However, AYAs tend to be less active during and after chemotherapy.

“Physical activity interventions are recommended to relieve symptoms and improve function,” Erickson said. “Few studies have explored symptoms and physical activity in AYAs during cancer treatment.”

Therefore, Erickson and colleagues are conducting the randomized PROMIS-29 trial which is designed to examine the effects of physical activity interventions for AYAs to help them self-manage fatigue. In her presentation, she described the symptoms and physical activity of young adults during the early months of chemotherapy to provide baseline data for the larger study.

Patients treated at the Froedtert Hospital/Medical College of Wisconsin Cancer Center and Children’s Hospital of Wisconsin who were aged 18 to 39 years and starting a chemotherapy regimen for any cancer diagnosis are eligible for the study.

To document their baseline physical activity, participants wore an accelerometer device for 7 days during chemotherapy administration to determine steps per day and the amount of time participants spent per day in light, moderate, and/or vigorous physical activity. In addition, symptom severity was surveyed on day 1 of a patient’s chemotherapy cycle.

The 21 AYAs were an average age of 33 years of age (range, 18-39 years); and majority were female (n = 15, 71%), white (n = 17; 81%), married (n = 12; 57.1%), and parents (n = 12; 57.1%). The AYAs were diagnosed with breast cancer (32%), lymphoma (31%), acute lymphocytic leukemia (25%), myeloma (6%), or melanoma (6%).

At baseline, the group averaged 4638 steps per day (range, 1318-11,572) with 233.35 minutes per day of light physical activity (range, 119-330), 16.08 minutes per day of moderate physical activity (range, 0.02-92), and no vigorous physical activity.

“These young adults were inactive during the early months of chemotherapy. We can measure that and compare that to an age-matched, national, healthy cohort. In that cohort, by average, young adults, males and females, had about 20 to 30 minutes of moderate physical activity a day, and this sample only had about 15,” said Erickson. “But there were various levels of physical activity in this sample. And their symptom scores were about average at the beginning of their chemotherapy regimen.”

For the PROMIS-29 profiling, a T score of 50 is considered average for the general US population, with a higher score being more of the concept, Erickson said. The mean standardized PROMIS-29 profile scores varied for physical function (49.48; range, 33.3-56.9), anxiety (56.33; range, 40.3-67.3), depression (52.27; range, 41-79.4), fatigue (55.86; range, 33.7-69.0), sleep disturbance (53.07; range, 37.5-66.0), ability to participate (49.56; range, 34.0-64.2), and pain interference (50.33; range, 37.3-64.2).

“It is interesting how their symptoms were about average,” Erickson said. “There is some evidence that, in particular, AYAs have higher symptom severity scores than other ages, but that didn’t look to be true in this beginning sample that I have. So, I will be interested to see how their related symptoms change over the months of treatment, and how that affects their physical activity.”

She is also interested to see what the AYA population impacted by chemotherapy treatment does with the remaining hours of their day, and how researchers can combat inactivity.

“If you think they had 4 hours of light physical activity, that means there about 20 hours filled with sedentary behavior and sleep,” Erickson said. “So how can we make sure we are looking more at their sleep and sedentary behavior, and prevent those minutes of inactivity?”

Lastly, Erickson noted she will continue to follow these patients for 8 months.

“It is important to look at how their physical activity changes during their months of cancer treatment,” she said. “The other concern is that they get caught in that cycle where they have fatigue and become less active and have more fatigue and become even more inactive. So, what I would like to see my intervention do is break that cycle of fatigue and try to maintain activity or prevent inactivity over the months of chemotherapy.”

Erickson J, Swartz A, Tokarek N. Physical Activity and Symptoms in Young Adults with Cancer in Early Months of Chemotherapy. Presented at: ONS 43rd Annual Congress; May 17-20, 2018; Washington D.C. 

https://ons.confex.com/ons/2018/meetingapp.cgi/Paper/3716

As part of a larger study, nurses found it is important for AYAs to remain physically active during and after cancer treatment.

Kristie Kahl