Oncology Nursing News’ Top ASCO Picks

We rounded up 5 stories from the 2022 ASCO Annual Meeting that are of most value to oncology nurses.

This year’s meeting highlighted advances in ovarian clear cell carcinoma, as well as significant differences in tolerability among different approved PARP inhibitors. Investigators also took an inside look at the driving factors behind medication non-adherence in older patients who were prescribed oral therapies, the impact of ribociclib dose reductions on overall survival in patients with hormone receptor–positive, HER2-negative, advanced breast cancer, and whether or not Vitamin D has prognostic value in determining a patient’s risk of developing chemotherapy-induced peripheral neuropathy.

Real-World Data Identify Significant Differences in Tolerability Among Approved PARP Inhibitors in Ovarian Cancer

David O’Malley, MD

Patients with ovarian cancer treated with FDA-approved PARP inhibitors had significant differences in the incidence of clinically relevant adverse events (AEs), according to results of a real-world analysis presented at the 2022 ASCO Annual Meeting.

The findings highlight differences in tolerability, use, and dose modifications associated with olaparib (Lynparza), niraparib (Zejula), and rucaparib (Rubraca) for patients treated with ovarian cancer between January 1, 2017, and December 31, 2020.

Crude results found that clinical events of interest (CEIs) were generally stable across calendar years, but were lower with olaparib vs niraparib for most years. Furthermore, the risk of any CEI, as well as time to PARP dose decrease and PARP dose discontinuation, was significantly different with niraparib compared with olaparib and with niraparib compared with rucaparib.

In a multivariable Cox regression analysis, the adjusted hazard ratio (HR) of any CEI with niraparib vs olaparib was 1.34 (95% CI, 1.19-1.52; P < .001), compared to 1.13 with rucaparib vs olaparib (95% CI, 0.96-1.33; P = .1318) and 1.19 with niraparib vs rucaparib (95% CI, 1.01-1.40; P = .0385). The risk of all-cause hospital admission with niraparib vs olaparib was 1.46 (95% CI, 1.15-1.84; P = .0016), compared to 1.38 with rucaparib vs olaparib (95% CI, 1.03-1.86; P = .0301) and 1.05 with niraparib vs rucaparib (95% CI, 0.79-1.40; P = .7257).

Adjusted HR for time to dose reduction with niraparib vs olaparib was 1.78 (95% CI, 1.43-2.22; P < .001), compared with 1.31 with rucaparib vs olaparib (95% CI, 0.97-1.75; P = .0744) and 1.37 with niraparib vs rucaparib (95% CI, 1.03-1.81; P = .0317). For treatment discontinuation, the adjusted HR was 1.73 with niraparib compared with olaparib (95% CI, 1.47-2.02; P < .001), 1.35 with rucaparib vs olaparib (95% CI, 1.09-1.66; P = .0056), and 1.28 with niraparib vs rucaparib (95% CI, 1.05-1.57; P = .0161).

“Tolerability, or how well patients cope with the [adverse] effects of treatment, is a key consideration when selecting a PARP [inhibitor],” David O’Malley, MD, professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine and the director of the Division of Gynecologic Oncology at the OSUCCC – James, and coinvestigators, wrote in a poster of the data. “Here we expand on earlier work to further explore real-world tolerability and dose changes in patients with ovarian cancer receiving PARP therapy in the [US]; we also investigate how many patients continue PARP [inhibitor] therapy without treatment gaps.”

Reference

1. O’Malley D, Arend RC, Alam N. Real-world use, tolerability, and dose modifications of PARP inhibitors in ovarian cancer. J Clin Oncol. 2022;40(suppl 16):5552. doi:10.1200/JCO.2022.40.16_suppl.5552

Patients With HR+/HER2- Advanced Breast Cancer May Reduce Ribociclib Dose Without Jeopardizing Outcomes

Dose modifications of ribociclib (Kisqali) did not demonstrate a negative effect on overall survival (OS) outcomes in postmenopausal patients with hormone receptor–positive, HER2-negative advanced breast cancer who received the therapy in combination with letrozole, according to a final protocol-specified OS analysis of the phase 3 MONALEESA-2 trial (NCT01958021).

Lowell Hart, MD, FACP

Results were presented in a poster by Lowell Hart, MD, FACP, scientific director of clinical research at Florida Cancer Specialists and Research Institute during the 2022 ASCO Annual Meeting.

A landmark analysis showed that the median OS among those who had at least 1 reduction 3 months into treatment was 63.1 months compared with 65.7 months among those with 0 reductions during that time frame (HR, 0.96; 95% CI, 0.68-1.36). Moreover, in a time-varying Cox regression analysis of OS by dose reduction, the median OS was 66.0 months (95% CI, 57.6-75.7) in the modification group and 60.6 months (95% CI, 42.5-79.2) in the standard group (HR, 0.87; 95% CI, 0.65-1.18).

OS outcomes were consistent with prior findings from the MONALEESA-3 (NCT02422615) and MONALEESA-7 trials (NCT02278120), suggesting that deviating from the recommended dose of 600 mg daily on a 3 weeks on/1 week off cycle in combination with endocrine therapy will yield a similar OS benefit. Notably, investigators determined that neither length of treatment nor timing of dose reduction changed these results.

Reference

1. Hart L, Bardia A, Beck T, et al. Impact of ribociclib dose modifications on overall survival in patients with HR+/HER2– advanced breast cancer in MONALEESA-2. J Clin Oncol. 2022;40 (suppl 16):1017. doi:10.1200/JCO.2022.40.16_suppl.1017

Vitamin D Insufficiency Predictive of Paclitaxel-Induced Peripheral Neuropathy in Early-Stage Breast Cancer

Baseline vitamin D insufficiency may be a prognostic factor for increased risk of chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving paclitaxel to treat early-stage breast cancer, according to a retrospective validation analysis of patients enrolled in the SWOG 0221 trial (NCT00070564).^1,2 Moreover, these findings may be especially meaningful for Black patients with breast cancer, as the results demonstrated that vitamin D insufficiency is more prevalent in this patient population.¹

The findings, which were presented in a poster by Lidia Schapira, MD, FASCO, professor of medicine at Stanford University School of Medicine, during the 2022 ASCO Annual Meeting, showed that patients with vitamin D insufficiency demonstrated a higher risk of CIPN.

Vitamin D insufficiency was defined as 20 ng/mL with higher levels signifying vitamin D sufficient status. Overall, the rate of grade 3/4 CIPN was 21% (n = 397) among patients with sufficient status compared with 14% (n = 794) among those with vitamin D insufficiency (odds ratio [OR], 1.57; 95% CI, 1.14-1.15; P = .005). After adjusting for covariates, the odds ratio was 1.39 (95% CI, 0.98-1.97; P = .066).¹

Notably, the findings also revealed that Black patients had a higher incidence of vitamin D insufficiency, which may correlate with higher incidence of CIPN. Compared with White patients enrolled in SWOG 0221, 77% of Black patients (n = 109) had vitamin D insufficiency compared with 28% of White patients (n = 997).¹

The rate of grade 3/4 CIPN among Black patients with vitamin D insufficiency (n = 84) was 31%. these patients were also less likely to be taking vitamin D supplements (P =.046). In an analysis comparing the association of vitamin D insufficiency with incidence of CIPN among Black patients vs White patients the odds ratio was 2.48 (95% CI, 1.57-3.86; P < .001).

“Chemotherapy-induced peripheral neuropathy is the major treatment-limiting and debilitating toxicity of paclitaxel,” the study authors wrote in the poster. “Prior retrospective studies suggest vitamin D insufficiency is associated with higher risk and severity of paclitaxel-induced [peripheral neuropathy].”

References

1. Chen CS, McCann SE, Budd GT, et al. Vitamin D insufficiency as a peripheral neuropathy risk factor in White and Black patients in SWOG 0221. J Clin Oncol. 2022;40(suppl 16):12023. doi:10.1200/JCO.2022.40.16_suppl.12023

2. Budd G, Barlow WE, Moore HCF, et al. SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. J Clin Oncol.2015;33(1):58-64. doi:10.1200/JCO.2014.56.3296

Forgetfulness A Significant Barrier to Oral Adherence in Elderly Patients With Prostate Cancer

Elderly patients with advanced prostate cancer who were prescribed enzalutamide (Xtandi) reported better adherence to oral treatment than those who were prescribed abiraterone, according to findings from a prospective trial of the Meet-URO network. However, the results, which were recently presented during the 2022 ASCO meeting, showed that forgetfulness is a potential barrier to adherence with this treatment.

Non-adherence rates were assessed by comparing the number of missed pills to the number of prescribed pills though pill counting, an overall estimate was given based on the median of individual values. The percentage of missed pills per prescribed pills was 5.2% in the abiraterone cohort compared with 4.2% in the enzalutamide cohort (P < .001). However, patients receiving enzalutamide were more likely to cite forgetfulness as their reason for non-adherence than their peers in the other cohort; the percentage of patients who cited forgetfulness as their reason was 42% (38 patients) vs 17% (4 patients), respectively (P < .001).

“Physicians tend to treat elderly and frailer [patients with] mCRPC with enzalutamide,” wrote study authors in the poster. “These [patients tend to be] more adherent to treatment, however, forgetfulness is a potential barrier.”

“Despite this, [abiraterone] conferred a longer progression-free survival [PFS] in our study population,” they wrote.

Reference

1. Rescigno P, Maruzzo M, Rebuzzi SE, et al. Adherence to oral treatments in elderly advanced prostate cancer patients, the ADHERE study: a prospective trial of the MEET-URO network.J Clin Oncol. 2022;40(suppl 16):12044. doi: 10.1200/JCO.2022.40.16_suppl.12044

Frontline Bevacizumab Prolongs PFS, OS in Ovarian Clear Cell Carcinoma

The addition of bevacizumab(Avastin) to first-line chemotherapy resulted in significant improvements in progression-free survival (PFS) and overall survival (OS) compared with platinum-based chemotherapy in patients with advanced ovarian clear cell carcinoma (OCCC), according to a retrospective analysis presented at the 2022 ASCO Annual Meeting.¹

OCCC is a rare histological type of epithelial ovarian cancer that is typically resistant to chemotherapy, accounting for its historically poor prognosis for patients. Most patients will have early-stage disease, but about 30% have advanced disease. Seki also noted that the frequency of OCCC is more common in Asian countries, especially in Japan.

Bevacizumab has shown an impact on treating patients with epithelial ovarian cancers and was first approved in Japan in November 2013 for the treatment of patients with ovarian cancer.² Moreover, A prior analysis in a small group of patients with OCCC showed that treatment with bevacizumab added to first-line chemotherapy led to a significant difference in PFS.³

Additionally, a study of 2 potential subtypes of OCCC by gene expression signatures suggested that patients with a mesenchymal type, where angiogenesis and the PI3K-AKT and IL-6 signaling pathways were activated, may benefit more from bevacizumab than those with more epithelial expression (HR, 0.5; P = .1978), despite higher stages of disease.⁴

“The addition of bevacizumab to platinum-based chemotherapy improved PFS and OS in [patients with] advanced OCCC,” said Toshiyuki Seki, MD, of the Department of Obstetrics and Gynecology, Kashiwa Hospital, The Jikei University School of Medicine, Chiba, Kashiwa, Japan. “The benefit was especially significant in stage IIIA and IIIB disease.”

References

1. Seki T, Tate S, Nishikimi K, et al. Bevacizumab in first-line chemotherapy to improve the survival outcome for advanced ovarian clear cell carcinoma: A multicenter, retrospective analysis. J Clin Oncol. 2022;40(suppl 16):5502. doi:10.1200/JCO.2022.40.16_suppl.5502

2. Anti-Cancer Agent “Avastin," Obtained Approval for Additional Indication of Ovarian Cancer. News release translation. Chugai Pharmaceutical Co., Ltd. November 22, 2013. Accessed June 6, 2022. https://bit.ly/3MlkMVR

3. Tate S, Nishikimi K, Matsuoka A, et al. Bevacizumab in first-line chemotherapy improves progression-free survival for advanced ovarian clear cell carcinoma. Cancers (Basel). 2021;13(13):3177. doi:10.3390/cancers13133177

4. Tan TZ, Ye J, Yee CV, et al. Analysis of gene expression signatures identifies prognostic and functionally distinct ovarian clear cell carcinoma subtypes. EBioMedicine. 2019;50:203-210. doi:10.1016/j.ebiom.2019.11.017