Background
Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent, but potentially serious, adverse event that can occur after exposure to bone-modifying agents (BMAs; e.g., ...bisphosphonates, denosumab, and antiangiogenic therapies). BMAs are typically used at higher doses to prevent skeletal-related events in cancer patients and at lower doses for osteoporosis/bone loss. MRONJ can cause significant pain, reduce quality of life, and can be difficult to treat, requiring a multiprofessional approach to care.
Methods
We reviewed the literature and guidelines to summarize a practical guide on MRONJ for nurses and other allied healthcare professionals.
Results
While there is a risk of MRONJ with BMAs, this should be considered in relation to the benefits of treatment. Nurses and other allied healthcare professionals can play a key role alongside physicians and dentists in assessing MRONJ risk, identifying MRONJ, counseling the patient on the benefit–risk of BMA treatment, preventing MRONJ, and managing the care pathway of these patients. Assessing patients for MRONJ risk factors before starting BMA treatment can guide preventative measures to reduce the risk of MRONJ. Nurses can play a pivotal role in facilitating multiprofessional management of MRONJ by communicating with patients to ensure compliance with preventative measures, and with patients’ physicians and dentists to ensure early detection and referral for prompt treatment of MRONJ.
Conclusions
This review summarizes current evidence on MRONJ and provides practical guidance for nurses, from before BMA treatment is started through to approaches that can be taken to prevent and manage MRONJ in patients receiving BMAs.
PURPOSE The After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) phase III study compares axillary lymph node dissection (ALND) and axillary radiation therapy (ART) in early breast cancer ...patients with tumor-positive sentinel nodes. In the ART arm, the extent of nodal involvement remains unknown, which could have implications on the administration of adjuvant therapy. In this preliminary analysis, we studied the influence of random assignment to ALND or ART on the choice for adjuvant treatment. PATIENTS AND METHODS In the first 2,000 patients enrolled in the AMAROS trial, we analyzed the administration of adjuvant systemic therapy. Multivariate analysis was used to assess variables affecting the administration of adjuvant chemotherapy. Adjuvant therapy was applied according to institutional guidelines. Results Of 2,000 patients, 566 patients had a positive sentinel node and were treated per random assignment. There was no significant difference in the administration of adjuvant systemic therapy. In the ALND and ART arms, 58% (175 of 300) and 61% (162 of 266) of the patients, respectively, received chemotherapy. Endocrine therapy was administered in 78% (235 of 300) of the patients in the ALND arm and in 76% (203 of 266) of the patients in the ART arm. Treatment arm was not a significant factor in the decision, and no interactions between treatment arm and other factors were observed. Multivariate analysis showed that age, tumor grade, multifocality, and size of the sentinel node metastasis significantly affected the administration of chemotherapy. Within the ALND arm, the extent of nodal involvement remained not significant in a sensitivity multivariate analysis. CONCLUSION Absence of knowledge regarding the extent of nodal involvement in the ART arm appears to have no major impact on the administration of adjuvant therapy.
In Europe, treatment of metastatic colorectal cancer (mCRC) with panitumumab requires prior confirmation of RAS wild-type mutation status. Two studies - a physician survey and a medical records ...review (MRR) - were conducted to evaluate the use of panitumumab and awareness among prescribing oncologists of the associated RAS testing requirements in clinical practice.
Both studies enrolled participants from nine European countries and were carried out in three consecutive rounds. Rounds 1 and 2 (2012-2013) examined KRAS (exon 2) testing only; the results have been published in full previously. Round 3 (2014-2015) examined full RAS testing (exons 2, 3, 4 of KRAS and NRAS) and was initiated following a change in prescribing guidelines, from requiring KRAS alone to requiring full RAS testing. For the physician survey, telephone interviews were conducted with oncologists who had prescribed panitumumab to patients with mCRC in the previous 6 months. For the MRR, oncologists were asked to provide anonymised clinical information, extracted from their patients' records.
In Round 3, 152 oncologists and 131 patients' records were included in the physician survey and MRR, respectively. In Round 3 of the physician survey, 95.4% (n = 145) of participants correctly identified that panitumumab should only be prescribed in RAS wild-type mCRC compared with 99.0% (n = 298) of 301 participants in Rounds 1 and 2, responding to the same question about KRAS testing. In Round 3 of the MRR, 100% (n = 131) of patients included in the study had confirmed KRAS or RAS wild-type status prior to initiation of panitumumab compared with 97.7% (n = 299) of 306 patients in Rounds 1 and 2 (KRAS only). Of those patients in Round 3, 83.2% (n = 109) had been tested for RAS status and 16.8% (n = 22) had been tested for KRAS status only.
Physicians' adherence to prescribing guidelines has remained high over time in Europe, despite the change in indication for panitumumab treatment, from KRAS to RAS wild-type mCRC. Additionally, this study demonstrates the uptake of full RAS testing among the majority of oncologists and pathologists.
Purpose
The study aim was to describe the management strategies used for severe infusion-related reactions (SIRs) and understand the impact of such events in oncology day hospitals in France, ...Germany, Spain, and the UK.
Methods
The study was based on qualitative telephone interviews and quantitative self-completion questionnaires and asked healthcare professionals about the impact of SIRs and consequent actions taken.
Results
The procedures to prevent and manage SIRs were similar across countries and settings. In all countries, they were part of a larger risk-assessment and adverse events-prevention process. Preventive measures included patient history, risk assessment, pre-medication, and close monitoring of high-risk patients. The management procedures comprised stopping the infusion, triggering of the emergency chain, administering corticosteroids ± antihistamines, and hospitalization if necessary. The recalled SIRs had important consequences to affected patients, healthcare providers, and hospital organizational plans. All affected patients needed to be monitored closely for a prolonged time, thus blocking hospital beds. 44% of patients needed to be hospitalized, 17% needed resuscitation, and one patient died of cardiac arrest immediately after the start of the infusion. Importantly, 82% of patients were not re-challenged with the presumedly SIR-causing regimen or re-challenged in a later line.
Conclusion
SIRs are unpredictable in nature, may have an extremely rapid onset, and are potentially fatal. Such events have a profound impact on the affected and surrounding patients, the care team and the organizational plan of the day-hospitals. Specific tools to reliably identify high-risk patients and predict the occurrence of events are needed.
Highlights • Systematic review and meta-analysis of bone metastases in those with breast cancer. • Included data from more than 175,000 patients with breast cancer. • 12% of patients with stage I–III ...breast cancer developed bone metastases. • Of those who developed any metastases during follow-up, 55% had bone metastases. • Of patients with metastatic breast cancer at study start, 58% had bone metastases.
Mutations in
pathway genes are poor prognostic indicators in patients with metastatic colorectal cancer. Plasma analysis of cell-free DNA is a minimally invasive and highly sensitive method to detect ...somatic mutations in tumors.
Plasma samples collected from panitumumab-treated patients in the ASPECCT study at baseline and safety follow-up (SFU) were analyzed by a next-generation sequencing-based approach for extended
mutant allele frequency as a continuous variable and their association with clinical outcomes and the mutational prevalence of 63 cancer-related genes. The correlation between patient outcome and baseline mutational status of
pathway genes was also examined.
Overall, 261 patients in the panitumumab arm had evaluable plasma samples. Patients with a higher
mutant allele frequency at baseline had worse clinical outcomes than those with a lower frequency (
< 0.001, Cox PH model); however,
mutations did not necessarily preclude patients from deriving benefits. The objective response rate (complete or partial response) was 10.8% for patients with baseline
mutations and 21.7% for those with
mutations. The 63-gene panel analysis revealed an increase in tumor mutational burden from baseline to SFU (
< 0.001, Wilcoxon signed rank test). Baseline mutations in
pathway genes, when analyzed both categorically and continuously, were associated with shorter survival.
When mutations in
pathway genes were analyzed continuously, higher mutant allele frequency correlated with poorer outcomes. However, extended
mutation, by itself, did not preclude clinical responses to panitumumab in a monotherapy setting.
Purpose
To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780).
Methods
Patients with previously untreated,
KRAS
exon 2 wild-type ...(WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour
RAS
status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR).
Results
One hundred seventy patients had
RAS
WT and 156 had
RAS
WT/
BRAF
WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the
RAS
WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 95% confidence intervals (CI) = 0.48–0.96;
p =
0.029) and
RAS
WT/
BRAF
WT (13.1 vs 10.1 months; HR = 0.61 95% CI = 0.42–0.88;
p =
0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 95% CI = 0.53–1.11;
p =
0.15) and 41.3 versus 28.9 months (HR = 0.70 95% CI = 0.48–1.04;
p =
0.08), in the
RAS
WT and
RAS
WT/
BRAF
WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 95% CI = 0.39–0.88;
p =
0.011) and DpR (65.0 vs 46.3%;
p =
0.0018) were improved in the panitumumab group. More panitumumab patients experienced ≥30% ETS at week 8 (64 vs 45%;
p =
0.052); ETS was associated with improved PFS/OS. No new safety signals occurred.
Conclusions
First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with
RAS
WT mCRC.
Highlights • EGFR inhibitors are better tolerated than chemotherapy but have specific toxicities. • Healthcare professionals must be aware of these characteristic adverse events. • Key prophylactic ...measures should be followed for patients receiving EGFR inhibitors. • Patient/caregiver education is essential for adherence to prophylactic measures. • Management of toxicities should be stepwise, based on the severity of symptoms.
Panitumumab is approved for RAS wild‐type metastatic colorectal cancer and was evaluated in Phase III (PRIME, NCT00364013) and Phase II (PEAK, NCT00819780) first‐line randomised studies. This ...retrospective analysis of these trials investigated efficacy and toxicity of panitumumab‐based maintenance after oxaliplatin discontinuation in RAS wild‐type patients. First‐line regimens were FOLFOX4 ± panitumumab in PRIME and mFOLFOX6 plus panitumumab or mFOLFOX6 plus bevacizumab in PEAK. Outcomes included median progression‐free survival (PFS) and overall survival (OS), from randomisation and oxaliplatin discontinuation, and toxicity. Overall, median duration of panitumumab plus 5‐fluorouracil/leucovorin (5‐FU/LV) maintenance was 21 (interquartile range: 11–41) weeks; that of 5‐FU/LV ± bevacizumab maintenance was 16 (6–31) weeks. Median OS from randomisation was 40.2 (95% confidence interval: 30.3–50.4) and 39.1 (34.2–63.0) months for panitumumab plus 5‐FU/LV maintenance and 24.1 (17.7–33.0) and 28.9 (21.0–32.0) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. Median PFS from randomisation was 16.6 (11.3–23.6) and 15.4 (11.6–18.4) months for panitumumab plus 5‐FU/LV maintenance and 12.6 (9.4–16.2) and 13.1 (9.5–16.6) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. From oxaliplatin discontinuation, median OS was 33.9 (24.7–42.8) and 33.5 (24.5–54.9) months for panitumumab plus 5‐FU/LV maintenance and 16.4 (12.4–24.1) and 23.3 (15.7–26.3) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively; PFS was 11.7 (7.8–19.2) and 9.7 (5.8–14.8) months and 7.1 (5.6–10.2) and 7.0 (3.9–10.6) months, respectively. The most frequently reported adverse events were rash, fatigue and diarrhoea. Maintenance of panitumumab plus 5‐FU/LV after oxaliplatin discontinuation was well tolerated and may be an acceptable treatment paradigm for patients demonstrating a good response to first‐line treatment. Prospective studies are warranted.
What's new?
Panitumumab is an anti‐EGFR antibody used in the treatment of RAS wild‐type metastatic colorectal cancer. But is it useful for long‐term therapy in these patients, especially after more toxic therapies like oxaliplatin are discontinued? In this retrospective analysis, the authors found that a maintenance regimen including panitumumab was well tolerated and may be associated with better outcomes than non‐panitumumab strategies. Patients who received panitumumab‐based maintenance therapy were also more likely to have had a good response to first‐line treatment. The results from this study indicate that further, prospective studies are warranted.
Purpose
To report exploratory analyses of early tumour shrinkage (ETS) and depth of response (DpR) in patients with
RAS
wild-type (WT) metastatic colorectal cancer (mCRC), receiving the first-line ...treatment in three randomised panitumumab trials.
Methods
Data from the PRIME (NCT00364013), PEAK (NCT00819780) and PLANET (NCT00885885) studies were included. Median DpR, the proportion of patients achieving ETS ≥ 20% or ≥ 30% at week 8, and the impact of ETS and DpR (including by category) on outcome were analysed. Factors associated with ETS and DpR and the optimal ETS/DpR cut-off values for predicting improved overall survival (OS) were assessed.
Results
Overall, 505, 170 and 53 patients had
RAS
WT mCRC in PRIME, PEAK and PLANET, respectively. Patients receiving panitumumab had higher ETS rates (≥ 30%: PRIME 59% vs. 38%; PEAK 64% vs. 45%) and greater DpR (PRIME: 54% vs. 46%; PEAK: 65% vs. 46%) than those receiving treatment without panitumumab. In multiple regression analyses, panitumumab treatment, liver-only metastases and WT
BRAF
status were consistently associated with improved ETS and DpR outcomes. Irrespective of treatment, ETS and DpR were associated with improved progression-free survival, overall survival and resection rates; most resections occurred in patients in the two highest DpR categories. In PRIME and PEAK, respectively, the optimal cut-offs for predicting improved OS were 32 and 34% for ETS, and 59 and 70% for DpR.
Conclusions
These exploratory analyses suggest that panitumumab is associated ETS and DpR benefits in patients with
RAS
WT mCRC and that achieving these endpoints during first-line treatment is linked with favourable outcomes.
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