Background

The goal of phase I trials is to determine adverse event (AE) profiles of new therapies. Typically, AEs are captured by clinicians, yet patient reported outcome (PRO) tools collect AEs which may be under reported. Our single center, prospective study aimed to validate PRO-CTCAE in phase I clinical trial patients (pts).

Methods

Pts eligible for phase I trials at Princess Margaret Cancer Centre were evaluated using tablet based, PRO-CTCAE with the full item library (n = 80) in addition to standard, matched clinician reported CTCAE grading of AEs at baseline (BL), mid cycle 1 (C1) and 2 (C2). Overall (BL + C1 + C2) totals were also assessed. Characteristics (age, gender, tumor group, ECOG, education), best response (using RECIST v1.1), and treatment information were collected. Comparative (kappa) statistics were used to assess agreement of patient and clinician reported AEs.

Results

Of 292 pts approached (05/2017 to 01/2019), 265 (91%) were consented and 243 (92%) were evaluable, with 552 surveys completed. Median age was 61 (range 18-82), 51% were female, and 79% were ECOG 1; with GI (31.7%), head and neck (13.2%), and breast (10.7%) as frequent tumor types. Pts were commonly treated with immune (66%) and/or targeted (21%), mono (35%) or combination (61%) therapy. PRO-CTCAE completion rates were high (98.7%), with fatigue (75%), pain (68%), and anxiety (54%) as often reported overall patient AEs. Common physician reported AEs were fatigue (41%), pain (39%) and insomnia (18%). Overall patient-clinician agreement (kappa), was poor for fatigue (0.12) and anxiety (0.08), and fair for pain (0.28). Clinician reported insomnia (0.2) was fair. Highest patient-clinician agreement was seen for dyspnea at BL (0.54), and edema (0.55) and rash (0.49) at C2. Despite patient reporting, clinicians did not report select AEs (palpitations, hiccups, vaginal dryness), and had poor overall agreement for cognitive (0-0.03), urinary (0.02-0.05), and mood (0.05-0.08) symptoms.

Conclusions

Completion of PRO-CTCAE was high in phase I trial pts. Clinician reported AEs had poor to fair agreement compared with PRO-CTCAE, suggesting under-reporting in phase I trials. This information could inform a phase I PRO survey to complement clinician reported AEs. Analyses are ongoing.

Legal entity responsible for the study

Drug Development Department, Princess Margaret Cancer Centre.

Funding

Has not received any funding.

Disclosure

A.A. Razak: Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (institution): CASI; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): BMS; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Amgen; Honoraria (self): Boehringer Ingelheim. A. Spreafico: Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: Oncorus; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Surface Oncology; Research grant / Funding (institution): Northern Biologics; Research grant / Funding (institution): Janssen Oncology/Johnson & Johnson. P. Bedard: Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Servier; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): SignalChem; Research grant / Funding (institution): PTC Therapeutics; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Lilly; Research grant / Funding (self): Pfizer. L.L. Siu: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Loxo; Advisory / Consultancy: Oncorus; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/MedImmune; Advisory / Consultancy: Morphosys; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy: GeneSeeq; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Seattle Genetics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Boehringer-Ingelheim; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Intensity Therapeutics; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Mirati. A.R. Hansen: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): GSK; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Boehringer-Ingelheim; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Karyopharm. All other authors have declared no conflicts of interest.

Background

The adverse events generated by immunotherapies are characterized by their wide diversity, unpredictability and reversibility by steroid used, and requires a delicate management. A collaborative organization of immunological toxicology management called ImmunoTOX (iTox) has been set up at Gustave Roussy to support physicians in their routine practice.

Methods

Descriptive study of all consecutive advice given by the ImmunoTOX committee at Gustave Roussy from Apr 6, 2016 to Jan 2, 2019. The iTox committee organizes a multidisciplinary meeting twice a month with organs specialists, oncologists, pharmacovigilants, radiologists, around prescribing physicians facing difficult to manage or unusual immune related adverse events (irAEs).

Results

The iTox committee delivered 398 pieces of advice for 356 patients (207 men and 149 women) receiving immunotherapies. Patients received anti-PD1 (55%) or anti-PDL1 (6%) given in monotherapy, or in combination with anti-CTLA4 (11%), or in combination with targeted therapy (11%), or another immunotherapy regimen (17%). The queries patterns for advices questioned the causal link (37%), rechallenge over G ≥ 3 (27%), or a complex clinical management (25%) or the possibility of initiating immunotherapy in a patient with comorbidities (10%). The iTox committee retained a causal link between the adverse event and immunotherapy in 273 of the 356 patients (77%). Of these 273 patients with irAEs, the grade of maximum severity was grade 1-2 in 112 (41%), grade 3-4 in 148 patients (54%), and irAE ultimately resulted in death in 13 (5%) patients. The organ categories mostly involved by requests were lung (21%), gastrointestinal (13%), liver (12%), musculoskeletal (10%) and neurological (8%). Over the study period, the 273 patients with irAEs led to 313 requests for advice that recommended systemic corticosteroids (n = 193, 62%) or a second immunomodulatory agents (n = 45, 14%).

Conclusions

These results should help cancer hospitals to further appreciate the current medical needs in their management of irAEs. By a specific management, patients with autoimmune comorbidities and rechallenge over G ≥ 3 could be regarded as precautions for use and not absolute contraindications.

Clinical trial identification

Commission Nationale de l’Informatique et des Libertés N°2098694v0.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J. Michot: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Cellgene; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (institution): Abbvie; Honoraria (institution): Xencor. J. Soria: Full / Part-time employment: MedImmune. C. Massard: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Leadership role: Lilly. All other authors have declared no conflicts of interest.

Background

The number of older people with cancer has been steadily increasing. Treating older people with anticancer treatments is challenging due to comorbidities, polypharmacy, poorer performance status and underrepresentation in clinical trials. An innovative service, GOLD, has been set up in our Cancer Centre. GOLD delivers comprehensive geriatric assessment (CGA) in older cancer patients to improve reversible factors and assist with anticancer treatment. We report outcomes of patients reviewed in GOLD clinic.

Methods

A one-stop GOLD clinic for older cancer patients was set up in 2016. From October 2016 to April 2018, 596 patients between 50-99 years old were reviewed. The majority (69.9%) were between 70-84 years. For the purpose of this analysis, a representative sample of 298 patients with similar characteristics (73% between 70-84 years) was selected; analysis included primary site of malignancy, treatment type and setting, referral reason and GOLD interventions. Cancer treatment outcomes were divided into patients who continued with planned treatment, and those who required other types of management.

Results

Referrals to GOLD were predominantly from gastrointestinal (28.5%), urology oncology (26.1%) and haematology (13.7%); lung, gynaecology, skin and breast accounted for the remaining 31.7%. The majority (92.7%) had single GOLD reviews. The following treatments were given: systemic anti-cancer therapy (SACT) with chemotherapy (51.6%), hormone therapy (21.1%), immune checkpoint inhibitors (6.8%), chemo-radiotherapy (6.8%) or tyrosine kinase inhibitors (3.6%). Of the 298 patients, 218 (73.2%) were able to proceed with their planned oncology treatment following GOLD review, start or continue SACT. 12.4% were deemed unfit and continued with best supportive care, 0.3% were referred to other specialities. 14.1% of the patients were on surveillance post anticancer treatment.

Conclusions

Collaborative working of oncologists with geriatricians may benefit older cancer patients with co-morbidities and age-specific problems. GOLD was largely “one-stop” and avoided multiple speciality referrals which may support cost-effectiveness whilst delivering more comprehensive care for older people with cancer.

Legal entity responsible for the study

The authors.

Funding

MacMillan Cancer Support.

Disclosure

All authors have declared no conflicts of interest.

Background

Improvement of treatment for metastatic colorectal cancer is still needed. We designed a double blinded randomized study to introduce triple drug chemotherapy – 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) as first-line treatment for metastatic colorectal cancer. The triplet might be more effective than doublet chemotherapy, but the use is limited by increased risk of serious adverse events (SAE). Tocotrienol – a vitamin E analogue - has neuroprotective and anti-inflammatory effects and may reduce toxicity. To investigate whether tocotrienol reduces toxicity of FOLFOXIRI, we randomized between addition of tocotrienol or placebo. The primary endpoint was ‘time to first SAE’ defined as a medical incident during treatment that leads to hospitalization or dead.

Methods

Patients with unresectable metastatic colorectal cancer were included for first-line treatment if 18-75 years, performance status (PS) 0-1 and adequate organ function. FOLFOXIRI was given in 8 cycles followed by 4 cycles of 5-fluorouracil. During and in up to 2 years, tocotrienol 300 mg x 3 daily or placebo was added.

Results

We included 70 patients and age (median 64 years, range 41-75), PS (69% PS = 0) and sex (39% female) was well balanced between the two arms. Median time to first SAE in the placebo arm was 3.7 months (95% CI 1.9-not reached (NR)), and in the tocotrienol arm the median was NR (95% CI 1.9-NR) with a hazard ratio of 0.70 (p = 0.29, 95% CI 0.36-1.36). The proportion of patients who had a SAE within seven months from treatment start was 53% vs. 43% for placebo and tocotrienol, respectively. Median PFS was 10.0 months in the placebo arm (95% CI 7.4-10.9) vs 9.7 months in the tocotrienol arm (95% CI 7.6-12.1) with a hazard ratio of 1.24 (p = 0.43). Response rate was 61% and 50% for placebo vs. tocotrienol (p = 0.49). Preliminary data shows a two-year survival rate of 51% (tocotrienol) and 54% (placebo), p = 0.92

Conclusions

This single center study of FOLFOXIRI combined with placebo or tocotrienol as first-line treatment of unresectable metastatic colorectal cancer showed a HR of 0.70 for postponing time to SAE but the difference was not statistically different. No differences in early efficacy outcomes were seen.

Legal entity responsible for the study

Lars Henrik Jensen.

Funding

Department of Oncology, Vejle Hospital.

Disclosure

L.H. Jensen: Research grant / Funding (institution), Corporate sponsored research: MSD; Research grant / Funding (institution), Corporate sponsored research: BMS; Research grant / Funding (institution), Corporate sponsored research: 2cureX. All other authors have declared no conflicts of interest.

Background

The management strategies regarding the strength of reactive topical corticosteroids have not been well evaluated in clinical trials. This FAEISS study is designed to confirm the superior efficacy of reactive topical corticosteroid strategies with serially ranking-DOWN from very strong levels compared with those with serially ranking-UP from weak levels for facial acneiform rash induced by EGFRI.

Methods

Pts with RAS wt mCRC were enrolled in the first registration. All pts received pre-emptive therapy with oral minocycline 100 or 200 mg/day and heparinoid moisturizer from the initiation of EGFRIs. Enrolled pts who developed facial acneiform rash within 8 weeks were randomized either to ranking-UP group (UP group) or ranking-DOWN group (DOWN group) (second registration) using minimization method for balancing institution, type of EGFRIs, and sex. Primary endpoint was incidence of Grade2 (moderate) or higher facial acneiform rash during 8 weeks after randomization.

Results

172 RAS wt mCRC pts, of whom 22 pts and 84 pts received cetuximab and panitumumab, respectively, were enrolled and 106 pts were randomized. There was no significant difference in the incidence of Grade 2 ≧ facial acneiform rash between UP group (18 times) and DOWN group (20 times) (stratified Wilcoxon’s rank sum test, one-sided: p = 0.86221). As for secondary end points, proportion of Grade3 or higher facial acneiform rash was 13.2% for UP group and 11.3% for DOWN group, showing no significant difference between the groups (Fisher’s exact test: p = 1.0000). There was no problem of safety concern in both groups.

Conclusions

Topical corticosteroids ranking UP from weak levels was confirmed to be standard therapy for the management of facial acneiform rash in pts with RAS wt mCRC. It would follow that minocycline and heparinoid moisturizer have a prophylactic efficacy while topical corticosteroids have a therapeutic efficacy for facial acneiform rash.

Clinical trial identification

UMIN000024113.

Legal entity responsible for the study

FAEISS Study Group.

Funding

AMED.

Disclosure

N. Yamazaki: Honoraria (self), Research grant / Funding (institution): Takarabio; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis. K. Kikuchi: Research grant / Funding (institution): POLA; Research grant / Funding (institution): Maruho. H. Fukuda: Honoraria (self): Taiho/chugai; Research grant / Funding (self): National Cancer Center. T. Hamaguchi: Honoraria (self), Research grant / Funding (institution): Ono; Honoraria (self): Takeda; Honoraria (self): Bayer. N. Boku: Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Research grant / Funding (institution): Ono; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb. T. Takenouchi: Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Novartis . T. Nishina: Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Merck Serono. S. Yoshikawa: Honoraria (self): Ono; Honoraria (self): Novertis; Honoraria (self): Bristol-Myers Squibb. K. Yamazaki: Honoraria (self): Chugai; Honoraria (self): Daiichi Sankyo. M. Takahashi: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ono; Speaker Bureau / Expert testimony: Daiichi Sankyo. T. Masuishi: Honoraria (self): Taiho; Honoraria (self): Merck Serono; Honoraria (self): Yakult Honsha. Y. Kiyohara: Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Ono; Honoraria (self), Research grant / Funding (institution): BMS. All other authors have declared no conflicts of interest.

Background

CMs are products used concurrently with conventional medicine, including natural products and homeopathy. CM use is prevalent amongst cancer patients, but the use in patients enrolled on P3T had yet to be studied. This study examined patient characteristics and outcomes of CM users enrolled in P3T conducted by the CCTG.

Methods

Data were acquired from six international P3T and included patients with metastatic breast (BR), colorectal (CRC), and non-small-cell lung cancers (LC) (MA.31, CO.17, 20 &23, BR.21 &26). Medications were independently reviewed by two authors to identify CM; discrepancies reviewed by a third author, and the final list was approved by consensus. Patient characteristics associated with CM use were identified with Chi-square and logistic regression. Propensity score stratification was conducted to compare between CM users and non-users for overall survival (OS), grade 3+ adverse events (AE) and quality of life (QOL) scales (EORTC-QLQ-C30).

Results

3446 patients were included (17.7% BR, 44.4% CRC, 37.8% LC). Of 24908 medications, 651 (2.6%) were considered CM and 20.4% of patients were CM users. CM use in LC was associated (p < 0.05) with ECOG performance status (PS) 0-1 (vs 2+), weight loss <5%, non-smoker, and Eastern Asian ethnicity. CM use in CRC was associated with age ≤65, PS 0-1 (vs 2+), fewer sites of metastases, and normal hemoglobin. CM use in BR was only associated with age <50. CM use did not affect time to global deterioration of QoL (hazard ratio (HR) 1.07 (p = 0.22, 95%CI 0.94-1.21)). CM use HRs for OS in LC, CRC, and BC P3T were 0.80 [p = 0.005; 95% CI (0.68-0.94)], 0.87 (p = 0.08; 95% CI (0.75-1.02)), and 0.85 (p = 0.35; 95%CI (0.61-1.19)), respectively.

Conclusions

The use of CM amongst patients enrolled in P3T is high. Patient’s using CM tend to be younger and have better PS. Worse QOL indices were associated with CM use, although time to deterioration and incidence of AE were not. HR for OS in the lung cancer trials favoured CM users, however, this should be interpreted with caution given the retrospective/post-hoc nature of this study and the more favourable baseline characteristics.

Clinical trial identification

MA.31- NCT00667251 CO.17- NCT00079066 CO.20- NCT00640471 CO.23- NCT01830621 BR.21- NCT00036647 BR.26- NCT01000025.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P.A. Bradbury: Honoraria (self), Advisory / Consultancy: AbbVie; Advisory / Consultancy: BI; Advisory / Consultancy: Merck; Honoraria (self): Lilly. C. Karapetis: Advisory / Consultancy: Merck Serono. L.K. Seymour: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): OSI Pharmaceuticals. All other authors have declared no conflicts of interest.

Background

Cancer patients are known to have higher average risk of suicide compared with general population. Acute clinical stressors, caused by deteriorating physical condition, may precipitate suicidal attempts in cancer patients.

Methods

Coroner’s files of all 4613 suicidal deaths of Hong Kong in 2012-2016 were reviewed. The files contained detailed reports on demographics, autopsy, police investigations and medical summary. Cancer was recorded in coroner’s files in 458 subjects (9.9%). Medical records of these 458 subjects were reviewed manually in a territory-wide electronic patient record system which covered 80% of all cancer care.

Results

More than half (56%) were diagnosed to have metastatic or incurable cancer at the time of suicide (advanced cancer patients). Advanced cancer patients had significantly higher health resources utilization compared with early-staged patients in terms of emergency room visit, clinic attendance and hospitalization. Emergency admissions, which represented symptom crisis, was temporally related to suicide. Ninety percent of suicide episodes occurred within 100 days of emergency admissions (median 12 days). Disclosure of bad news may represent another emotional stressor. Among advanced cancer patients, suicide occurred at a median time of 6 months after disclosure of bad news of metastases (median 182 days, interquartile range (IQR) 46-534 days). Suicide occurred at 2 months after the bad news of cessation of active cancer treatments (median 60 days, IQR 24-196 days). For psychiatric risk factors, advanced cancer patients had lower rate of psychiatric diagnosis compared with early-staged cancer patients (12.5% vs 23.7% p = 0.003). Similar trend was observed in other factors including gambling, debt and history of self-harm (2.3% vs 0.0%, p = 0.03; 2.8% vs 0.3%, p = 0.02; 4.4% vs 1.3%, p = 0.08 respectively).

Conclusions

Emergency admissions and bad news disclosure represent acute stressors that may precipitate suicidal attempts in cancer patients. Such temporal relationship was particularly strong in advanced cancer patients, suggesting a critical window for suicidal prevention interventions.

Legal entity responsible for the study

The authors.

Funding

The Hong Kong Jockey Club, Li Ka Shing Foundation.

Disclosure

T.C. Lam: Research grant / Funding (self): Roche; Research grant / Funding (self): Mundipharma. All other authors have declared no conflicts of interest.

Background

Fear of cancer recurrence (FCR) is an important psychological trauma that has been associated with reduction in the quality of life, disruptions in the level of adjustment, emotional distress and anxiety. The purpose of the study is to evaluate the impact of patient–physician relationship on FCR.

Methods

The study was designed as a multicenter survey study. The cancer survivors who were under remission, were evaluated with structured questionnaires. Patient–physician relationship (PPR) scale in which higher scores indicate better relationship and FCR inventory were used.

Results

Between January-April 2019, 1580 patients were evaluated. The median age was 57.0(19-88) and 66% were female. There was high level of FCR scores in 51% of participants. There was a negative correlation between PPR and FCR scores (r= -0.134, p < 0.001). In multivariate analysis; young age (OR = 1.46 CI(95%) 1.1-1.8, p = 0.002), female gender (OR = 1.93 CI(95%) 1.5-2.4, p < 0.001), history of non-routine imaging (OR = 1.8 CI(95%) 1.4-2.4, p < 0.001) and worse PPR (OR = 1.31 CI(95%) 1.07-1.6, p = 0.009) were associated with high levels of FCR.Table: 1617PD

The multivariate analysis of factors associated with high FCR scores

Conclusions

It is the first data showing the adverse impact of worse PPR on FCR. The strategies to improve the PPR should be practiced. In addition, the cancer survivors who are under the risk of FCR, should be evaluated and managed.

Legal entity responsible for the study

Ali Alkan.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.