Background

The present analysis was done to estimate the 5-year outcomes and late adverse events of locally advanced sinonasal tumours treated with induction chemotherapy followed by local therapy.

Methods

Twenty-five patients with locally advanced esthesioneuroblastoma or sinonasal neuroendocrine tumours treated between August 2010 to August 2014 with induction chemotherapy followed by local therapy were selected. The 5-year outcome and late adverse events (CTCAE version 4.02) were noted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. COX regression analysis was used to identify factors impacting PFS and OS.

Results

The median follow-up was 5.15 years. The 5 year PFS in esthesioneuroblastoma cohort and in SNEC cohort was 63.5 %( 95%CI 28.9-84.7) and 34.6 % (95%CI 10.1-61.1) respectively (P=0.1). The only factor impacting PFS on multivariate analysis was a response to neoadjuvant chemotherapy (p=0.033). The 5 year OS in esthesioneuroblastoma cohort and in SNEC cohort were 91.7% (95%CI 53.9-98.9) and 46.2% (95%CI 19.2-69.6) respectively (p=0.024). Any grade late adverse event was seen in 20 patients (80%). Metabolic late adverse events were seen in 19 patients (76%).

Conclusions

Neoadjuvant chemotherapy in advanced sinonasal cancers is associated with improvement in 5-year outcomes. However, late side effects especially metabolic are seen in these patients and should be evaluated during follow up.

Legal entity responsible for the study

Tata Memorial Hospital.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

Palliative care services are bieng provided to advanced cancer patients, and have traditionally included symptom directed therapy, counselling regarding goals of care and discussions centered around aggressiveness of care. An early palliative mliaison is bieng offered to patients with recently diagnosed tumours, but the ambit, purview and scope of these services has remained essentially unchanged.

Methods

Details of 127 patients admitted to the ward between over the course of three months were recorded and analysed.

Results

Analgesic titration (54 percent), interventional pain management (15 percent) and provision of supportive care services (23 percent) were the most common indications for admission. 44/123 patients (35.7 percent) received services which can be considered to be within the purview of supportive care. Bisphosphonate infusion for prevention of skeletal related events (12), pigtail catheter insertion for malignant pleural effusion (4), ultrasound guided therapeutic paracentesis (5), octreotide infusion for symptom control in neuroendocrine tumours and malignant bowel obstruction (3), management of difficult to control symptoms including dyspnoea and pain, malignant bowel obstruction (2), chemotherapy related complications (including febrile neutropenia, mucositis and diarrhea) were among services provided upon inpatient admission. 3 patients recieved chemotherapy. 13/127 recieved consultation liasion during their stay in the ward. Medical oncology liaison was the most commonly sought. The most commonly prescribed opioid was morphine followed by fentanyl and tramadol. Average duration of stay was 1.2 days with the longest admission lasting 5 days. The duration of stay was significantly longer for those who also recieved supportive care (p<0.01). Morphine equivalent daily dose, number of medications prescribed and Eastern cooperative oncology group performance status did not have any effect on the duration of stay.

Conclusions

The nature of services provided under the purview of this model, has the potential to ignite a larger debate on the impending and urgent need to redefine the scope of conventional Palliation.

Legal entity responsible for the study

Rahul D. Arora.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

It is known that breast cancer is a complex heterogeneous disease due to the presence or absence of overexpression of receptors on the surface of tumor cells that correlate with the presence of penetrant mutations. Malignant neoplasms are considered as genetic diseases if they are characterized by multiple mutations in the genome, or epigenetic changes at the DNA level. Hereditary forms of malignant neoplasms occupy a special position due to their frequent development at a young age.

Methods

The study was carried out using next-generation sequencing-NGS. A genetic blood test was performed on 30 patients with breast cancer.

Results

As a result, highly penetrant mutations in the BRCA1, BRCA2, CHEK2, PALB2, RAD50 genes were revealed in 30 patients. Of the total share of probands in the BRCA1 gene mutations were detected with a mutation of 5382insC - 12 patients, c.3143delG- 3. In the BRCA2 gene of patients mutation c.6621_6622del- in 2 people and s. -39-1_-39delGA- in 1 patient. Using IHC a basal-like subtype breast cancer was established in all patients. The mutations were detected in the CHEK2 gene in 5 patients: c.470T> C- in 3 patients with a luminal B (HER2 positive) subtype; c.444 + 1G> A- in 2 patients with HER2 positive (non-luminal). In the PALB2 gene of cases: all 4 people with a basal-like subtype with the 1592delT mutation. The mutations c. 2157delA were detected in the RAD50 gene in 3 patients: of which 2 had luminal B (HER2 negative), 1 had luminal A subtype of breast cancer.

Conclusions

A next-generation sequencing method has significantly improved the efficiency of detecting mutations in the genes responsible for hereditary breast cancer. Pathogenic mutations in the BRCA1 / 2, CHEK2, PALB2, RAD50 genes were found of patients with a hereditary feature of the disease (proband has 1 to 3 blood relatives with malignant neoplasms). The identification of highly penetrant mutations in probands allowed us to determine their relatives, the expectable carriers of mutations, which were informed of the need genetic counseling.

Legal entity responsible for the study

Sultanbaev Alexander.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated non-small cell lung cancer (NSCLC). However, some patients show intrinsic resistance and an insufficient response to osimertinib. Increased expression of the anexelekto (AXL) protein in tumors is reported to be associated with poor prognosis in patients with several types of cancer. We previously reported the crucial role of the AXL pathway in the intrinsic resistance to EGFR-TKIs in EGFR-mutated NSCLC cells. Moreover, AXL overexpression in EGFR-mutated NSCLC specimens was negatively associated with the therapeutic efficacy of first- and second-generation EGFR-TKIs. However, the relationship between AXL expression in tumors and the therapeutic efficacy of osimertinib is still unclear.

Methods

We retrospectively enrolled 30 patients with advanced or relapsed NSCLC with EGFR-activating mutations from four institutions in Japan. All patients were administered osimertinib as the first-line treatment between August 2017 and March 2019.

Results

Twenty-two (73.3%) patients were female; 21 (70.0%) patients had never smoked. The median age of patients was 71.0 years (range, 44–88 years of age). The EGFR-activating mutations were deletion in exon 19 in 16 (53.3%) patients; L858R missense mutation in exon 21 in 12 (40.0%) patients; and other types in 2 (6.6%) patients. High (3+), intermediate (2+), low (1+), and no (0) pre-treatment expression of AXL in tumors was observed in 2 (6.7%), 4 (13.3%), 12 (40.0%), and 12 (40.0%) patients, respectively. The maximal tumor shrinkage rate following osimertinib treatment in the patients with AXL expression scores of 0 and 1+ was higher than that in patients with AXL expression scores of 2+ and 3+ (44.12% vs. 25.93%, p = 0.094).

Conclusions

Pre-treatment AXL expression in tumors may be a promising predictor of osimertinib treatment efficacy in patients with EGFR-mutated NSCLC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Yamada: Research grant/Funding (self): Pfizer Inc.; Research grant/Funding (self): Ono Pharmaceutical Co., Ltd; Research grant/Funding (self): Chugai Pharmaceutical Co., Ltd; Research grant/Funding (self): Takeda Pharmaceutical Co., Ltd. S. Atagi: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squib; Honoraria (self): Hisamitsu; Honoraria (self): Kyowa Hakko Kirin; Research grant/Funding (institution): F. Hoffmann-La Roche. K. Takayama: Honoraria (self), Research grant/Funding (self): Chugai-Roche Co.; Research grant/Funding (self): Ono Pharmaceutical Co.; Honoraria (self): AstraZeneca Co.; Honoraria (self): MSD-Merck Co.; Honoraria (self): Eli Lilly Co.; Honoraria (self): Boehringer-Ingelheim Co.; Honoraria (self): Daiichi-Sankyo Co. All other authors have declared no conflicts of interest.

Background

Uncommon EGFR mutations show heterogeneity in their EGFR TKI sensitivities.¹ Afatinib has shown broad inhibitory activity against uncommon mutations in vitro,¹ and clinical activity against major uncommon mutations (G719X/L861Q/S768I).² However, clinical data regarding the efficacy of afatinib against other uncommon EGFR mutations are lacking, particularly between ethnicities.

Methods

This pooled analysis assessed afatinib activity in Asian/non-Asian, EGFR TKI-naïve pts with NSCLC and uncommon EGFR mutations, treated in RCTs and real-world studies. Uncommon mutations were classed as: de novo T790M; exon 20 insertions (Ins20); major uncommon mutations (G719X/L861Q/S768I); compound mutations (≥2 uncommon mutations); and other uncommon mutations. Key endpoints were overall response rate (ORR), duration of response (DoR), and time to treatment failure (TTF).

Results

Of the 178/120 Asian/non-Asian pts with uncommon EGFR mutations, 62/35% had a major uncommon mutation (G719X only: 20/20%; L861Q only: 26/8%; S768I only: 3/4%), 16/39% had an Ins20 mutation. Clinical activity (Asian/non-Asian) was observed against major uncommon mutations (ORR: 66/59%; median DoR: 14.7/15.9 mos; G719X: 62/65%; L861Q: 60/50%; S768I: 80/25%), compound mutations (ORR: 81/100%; median DoR: 11.5/18.6 mos) and other uncommon mutations (ORR: 79/60%; median DoR: 9.0/10.7 mos). Some pts with Ins20 responded (21/23%). TTF was longest in pts with compound mutations, particularly non-Asian pts (median 18.5 mos).

Conclusions

Afatinib is effective in pts with NSCLC with major uncommon and compound EGFR mutations, with broad activity against other uncommon EGFR mutations and some Ins20 mutations, unaffected by ethnicity. Asian pts appeared to have a high proportion of major uncommon mutations, known to be highly sensitive to afatinib.^{2 1.} Kohsaka S, et al. Sci Transl Med 2017;9:eaan6566 ^2. Yang JC, et al. Lancet Oncol 2015;16:830‒8 Table: 395P

Editorial acknowledgement

Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Nadia Fowler, of GeoMed, an Ashfield company, part of UDG Healthcare plc.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

J.C-H. Yang: Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche/Genentech; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: MSD Oncology; Honoraria (institution), Advisory/Consultancy: Merck Serono; Honoraria (institution), Advisory/Consultancy: Celgene; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy: Yuhan; Honoraria (institution), Advisory/Consultancy: Hansoh; Honoraria (institution), Advisory/Consultancy: Brueprint Medicines; Honoraria (institution), Advisory/Consultancy: Daiichi Snakyo; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Takeda Oncology; Honoraria (institution), Advisory/Consultancy: Incyte; Honoraria (institution), Advisory/Consultancy: H: Boehringer Ingelheim; Roche; MSD; AstraZeneca; Novartis; Bristol-Myers Squibb; Ono Pharmaceutical; Takeda Oncology; Eli Lilly; Pfizer. M. Schuler: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Honoraria (self): Amgen; Honoraria (self): MSD; Honoraria (self): Pierre Fabre. S. Popat: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AZ; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Guardant Health; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Paradox; Research grant/Funding (institution): Ariad. S. Miura: Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Taiho Pharma; Speaker Bureau/Expert testimony: Ono Pharma; Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony: Kyowa Hakko Kirin. S. Heeke: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Qiagen; Travel/Accommodation/Expenses: Roche. A. Passaro: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Dako. K. Park: Advisory/Consultancy: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AZ; Advisory/Consultancy, Speaker Bureau/Expert testimony: BI; Advisory/Consultancy: BMS; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: JNJ; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Research grant/Funding (self): MSD Research. E.S. Kim: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Takeda; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.

Background

Breast cancer prognostic factors vary from pathological grades, hormonal sensitivity, stage and LN metastasis. Results from recent studies discuss primary location as survival indicator but its significance still unclear. With SEER database registry in place, a rich source for data collection with differentiating breast cancer sites and primary location. With analysis of these data, the effect of cancer's primary origin on breast cancer survivorship would be more comprehensive.

Methods

Using SEER*stat 8.3.6 program, Based on Incidence - SEER Research Data, 9 Registries, Nov 2019 Sub (1975-2017), patients diagnosed with breast cancer (site recode ICD-O-3) between 1975-2017 are selected. Case listing session was done with extraction patients year of diagnosis, survival time in months, laterality, and primary site. Cox regression was done using IBM SPSS statistics 25. p-value <0.001 is considered significant.

Results

720272 patients were involved in analysis (50.9% left:49.1% right origin of primary). Median survival time for the cohort was 185 months(95% CI:184.4:185.5). Left side malignancy showed a significantly less positive effect on survival than right originated ones (HR, 0.988; 95% CI, 0.982–0.995). The upper and lower inner quadrants show a significantly higher effect on survival (HR, 1.877; 95% CI, 1.797–1.960) and 1.761(1.685). (HR, 1.761; 95% CI, 1.685–:1.842) respectively P-value <0.001. Table: 27P

Conclusions

Upper and lower inner quadrants show the best survival for patients diagnosed with breast cancer. The primary site of malignancy in breast cancer appears to be a good predictive value of survival and can be used as a rough method to predict patients` prognosis. More Data extraction, analysis, and interpretation of overall and cause-specific survival are recommended for more knowledge about the primary site in depth.

Legal entity responsible for the study

Mohamed Alaa Gouda.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

Apatinib, a novel treatment option for chemotherapy-refractory advanced gastric cancer (AGC), has not yet been evaluated in patients with locally AGC. This trial investigated the efficacy and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally AGC.

Methods

Patients with M0 and either T2-T4 or N+ disease received apatinib (500 mg orally once daily on days 1-21 and discontinued in the last cycle) plus SOX (S-1, 40-60 mg orally twice daily on days 1-14; oxaliplatin, 130 mg/m2 intravenously on day 1) given every 3 weeks for 2-5 cycles. D2 gastrectomy was performed 2-4 weeks after the last cycle. To further compare the efficacy and safety between apatinib plus SOX (ASOX group) and SOX alone (SOX group), we reviewed historical control patients receiving SOX as neoadjuvant chemotherapy at the central center. The primary end point was the R0 resection rate.

Results

Between July 2017 and June 2019, 48 and 58 patients were enrolled in the ASOX and SOX groups, respectively. Forty patients in the ASOX group (83.3%) and 47 patients in the SOX group (81.0%) underwent surgery, with R0 resection rates of 75.0% and 67.2%, respectively (P=0.382). The proportion of patients with T downstaging in the ASOX group was significantly higher than that in the SOX group (36.4% vs 18.5%, P=0.036). For patients with target lesions, the radiological response rate was significantly higher in the ASOX group (75.0% vs 38.5%, P=0.015). Moreover, the ASOX group was associated with significantly higher proportions of patients achieving major pathological response (25.0% vs 10.3%, P=0.046). Grade 3 toxicities occurred in 33.3% of the ASOX patients, and no grade 4 toxicities or drug-related deaths were observed.

Conclusions

Apatinib combined with SOX showed promising efficacy with an acceptable safety profile as the first-line neoadjuvant treatment for locally AGC.

Clinical trial identification

NCT03192735.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

Background

Hepatocellular carcinoma (HCC) patients with major vascular invasion (MVI) were generally recommend systemic treatment by guidelines, while some data showed R0 resection can improve survival than local treatment. Conversion therapy using immune checkpoint inhibitors may benefit these patients in the context of cancer immunotherapy. Here we report a prospective real-world study of PD-1 inhibitors in combination with tyrosine kinase inhibitors (TKIs) as a conversion therapy for HCC with MVI.

Methods

Briefly, the main inclusion criteria of the study (ChiCTR1900023914) was: Aged 18 to 75 years HCC patients diagnosed pathologically and/or radiologically, with at least one measurable lesion (mRECIST) and MVI. The criteria for Successful Conversion: 1. Child-Pugh score < 7. 2. ECOG PS score ≤1. 3. No extrahepatic lesion. 4. Intact vascular structure of the reserved liver and sufficient FLR.

Results

70 Patients were screened, and 39 patients enrolled in the study by May 20, 2020. Among them 35 patient accepted the combination therapy (Primary HCC n=31, Recurrence after local treatment n=4), in which 30 patients with PVTT, 2 with venous tumor thrombi and 3 with both. A total of 33 patients were assessable. The response evaluation according to mRECIST standard was in table below. Successful conversion rate based on radiology was 42.4% (14/33). Table: 174P

Summary of response evaluation and conversion rate

The subsequent salvage surgery was all en-bloc R0 resection of both tumor and PVTT. No complications beyond Clavien-Dindo level III or postoperative mortality were observed. The median follow-up time was 7.2 months. The median relapse free survival and median overall survival was 3.9 months and 6.5 months respectively. Patients with pPD had a worse prognosis.

Conclusions

The combination therapy of PD-1 inhibitors and TKIs can be reviewed as a reasonable and promising conversion therapy option for advanced HCC with safety and effectiveness. Furthermore, pathology can confirm the response evaluation and guide subsequent treatment more precisely.

Clinical trial identification

ChiCTR1900023914.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Afatinib is an efiective treatment for patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), however, its toxicities often require dose modifications. The aim of this study was to assess the eficacy and safety of low dose afatinib monotherapy in patients with EGFR mutation-positive NSCLC.

Methods

This study was a multicenter, single-arm, open-label phase II trial. Treatment-naïve patients with advanced NSCLC positive for common EGFR mutations received afatinib in a dose of 20mg/day. The same dose was continued unless the tumor had grown. The primary endpoint (PE) was progression-free survival (PFS) The threshold median PFS was 9.2 months and the expected median PFS 13.8 months.

Results

From March 2017 through September 2018, 53 patients were enrolled from 21 institutions in Japan. The median age was 70 years (range, 37–85), and 28 patients (52.8%) were women. EGFR mutation subtypes included exon 19 deletion (56.6%) and L858R point mutation (43.4%). Most patients had a performance status of 0 or 1 (86.8%). As of the data cut-ofi date of March 2020, the median follow-up was 20.8 months. The median PFS, time to treatment failure and overall survival were 12.6 months (95% CI: 9.7–14.3), 18.6 months (95%CI: 16.0-21.2) and not reached. The PE was met. The objective response and the disease control were 66.6% (95% CI: 51.7-78.5) and 92.5% (95% CI: 81.8-97.9). Adverse events (AEs) of grade 3 or higher occurred in 12 patients (22.6%) including diarrhea in 4 patients (7.5%) that was lower than that observed in phase III studies of afatinib using 40 mg. Eight of 19 patients (42.1%) had T790M resistant mutation in plasma and tissues. Afatinib plasma concentrations at 9 days after the start of administration had no correlations with clinical outcomes and AEs including diarrhea.

Conclusions

Low dose afatinib would be considered as one of standard therapy for EGFR mutation-positive NSCLCs because of promising clinical eficacy and good tolerability.

Legal entity responsible for the study

Thoracic Oncology Research Group.

Funding

Has not received any funding.

Disclosure

K. Kubota: Honoraria (self): Chugai Pharmaceutical, Taiho Pharmaceutical, MSD, Nippon Boehringer Ingelheim, Bristol-Myers Squibb, kyowa-hakko Kirin, AstraZeneca, Ono Pharmaceutical; Research grant/Funding (institution): Ono Pharmaceutical, Nippon Boehringer Ingelheim. K. Naoki: Speaker Bureau/Expert testimony: Nippon Boehringer Ingelheim; Research grant/Funding (institution): Nippon Boehringer Ingelheim; Spouse/Financial dependant: Nippon Boehringer Ingelheim. A. Bessho: Honoraria (self): Nippon Boehringer Ingelheim. K. Minato: Research grant/Funding (institution): Taiho Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb. N. Seki: Honoraria (self): AstraZeneca, Nipppon Boehringer Ingelheim, Eli Lilly Japan, Daiichi Sankyo, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical; Research grant/Funding (self): Nihon Medi-Physics, Nippon Boehringer Ingelheim; Research grant/Funding (institution): AstraZeneca. T. Tokito: Honoraria (self): AstraZeneca, Chugai Pharmaceutical, MSD. N. Furuya: Honoraria (self): Eli Lilly Japan, Chugai Pharmaceutical, AstraZeneca, Bristol-Myers Squibb, Taiho Pharmaceutical, NipponBoehringer Ingelheim. H. Hayashi: Research grant/Funding (institution): Nippn Boehringer Ingelheim. H. Iihara: Research grant/Funding (institution): 19 飯原 大稔 附随研究 \"岐阜薬科大学 岐阜大学医学部附属病院” Nippon Boehringer Ingelheim. H. Okamoto: Research grant/Funding (institution): Takeda, MSD, Ono Pharmaceutical, AstraZeneca, Merck, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol-Myers Squibb, Eli Lilly Japan, Daiich Sankyo. All other authors have declared no conflicts of interest.

Background

Mucositis is one of the most common oral complications arising in cancer patients receiving chemotherapy and/or radiotherapy. The pain and distress of mucositis can be enough to cause disability during the course of treatment. Vitamin E has been found to have antioxidant and free radical scavenging properties which can reduce inflammation. To date, vitamin E supplementation in the form of tablets or pastes have been tried with different levels of success in several trials, however, there is no clear recommendation for its use. This study was done to obtain a more precise estimate of the efficacy of vitamin E on radiotherapy and chemotherapy-induced mucositis, in the hopes of providing an easily available, inexpensive but effective treatment for this condition.

Methods

A systematic search of Pubmed, Embase, Cochrane, Clinical trials databases and hand search were utilized to identify randomized controlled trials (RCTs) dated until December 2019, investigating the efficacy of oral or topical vitamin E in reducing oral mucositis in cancer patients receiving chemotherapy or radiotherapy. Using the random effects model, pooled Odds Ratio (OR) with 95% confidence intervals (CI) were calculated in measuring the incidence of improvement or resolution of oral mucositis.

Results

Four RCTs were included (N=171). The pooled rate of mucositis resolution was significantly higher in the group treated with Vitamin E (84.7% vs 51.2%), with an odds ratio of 6.04 (95% CI 2.46-14.84, p < 0.0001). Heterogeneity between the studies was minimal (I² 0-20%). Vitamin E was well-tolerated and there were no severe adverse effects reported in the studies.

Conclusions

The results showed that vitamin E (topical or oral) was significantly associated with higher rates of improvement of oral mucositis among solid cancer patients who underwent chemotherapy or radiotherapy. Our results suggest that vitamin E can be considered a simple, non-toxic, yet effective therapy for oral mucositis. Subgroup analysis based on type and dose of vitamin E administration, type of anti-tumor treatment, and type of cancer can be done once with additional studies in the future.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

In the phase III RESORCE trial, regorafenib improved overall survival (OS) vs placebo in pts with uHCC who progressed on sorafenib. The international, prospective REFINE study was designed to evaluate regorafenib in pts with uHCC in routine practice. We present interim results for pts enrolled in REFINE in Korea, China, and Taiwan.

Methods

REFINE is an ongoing observational study that recruited patients with uHCC for whom a decision to treat with regorafenib was made by the treating physician prior to enrollment according to the local health authority approved label. A planned interim analysis was performed when the first 500 pts in the global cohort had been observed for ≥4 months. The primary aim is to assess treatment-emergent adverse events (TEAEs; NCI-CTCAE v4.03). Secondary endpoints include OS, progression-free survival, and tumor response. Tumor response and progression are assessed per investigator according to local standard.

Results

In the interim analysis, a total of 182 pts were enrolled from Korea (n=127; 70%), China (n=48; 26%), and Taiwan (n=7; 4%). The median age was 60 years (range 21–90); 80% were male. At study entry, proportions of pts with ECOG performance status 0/1/≥2 were 37%/49%/5%; proportions with Child–Pugh A/B/C class were 70%/5%/1% (missing/not evaluable: 24%). The initial daily regorafenib dose was 160 mg in 70% of pts and 120 mg/80 mg in 14%/15%; 1 pt started at 40 mg. The mean initial daily dose was 142 mg (standard deviation 31). Median treatment duration was 3.2 months (interquartile range 1.9–9.3). The most frequent TEAEs (reported in ≥5% patients) are shown in the table. Effectiveness results will be presented.

Conclusions

In this interim analysis of pts from Asia in the observational REFINE study, the TEAEs reported were consistent with those reported in the phase III RESORCE trial, although incidence rates of some TEAEs were lower than in RESORCE Table: 173P

Clinical trial identification

NCT03289273.

Editorial acknowledgement

Editorial assistance in the writing of this abstract was provided by Jennifer Tobin of OPEN Health Medical Communications (Choice), with financial support from Bayer.

Legal entity responsible for the study

Bayer.

Funding

Bayer.

Disclosure

H.Y. Lim: Advisory/Consultancy: Bayer; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ono Pharmaceutical. Y.J. Kim: Honoraria (self): Eisai; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (self): BTG; Honoraria (self): Bayer; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy, Resarch grant/Funding (self): Gilead Sciences; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Roche. Y-H. Huang: Advisory/Consultancy: Gilead Sciences; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy: Bayer. C-H. Hsu: Honoraria (self), Advisory/Consultancy: Bristol-Meyers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Genentech; Advisory/Consultancy: Merck Serono. H.C. Lee: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Bayer; Research grant/Funding (self): Roche; Research grant/Funding (self): Merck; Research grant/Funding (self): Bristol-Myers Squibb. S. Fiala-Buskies: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bayer. S. Kapur: Full/Part-time employment: Bayer. All other authors have declared no conflicts of interest.

Background

SPARTAN is a phase III trial that evaluated the efficacy of APA vs PBO in pts with nmCRPC with a prostate-specific antigen doubling time of ≤ 10 mo. At primary analysis, APA significantly improved metastasis-free survival and extended time to metastasis, progression-free survival, and time to symptomatic progression vs PBO (Smith MR, et al. N Engl J Med. 2018) while preserving health-related quality of life (Saad F, et al. Lancet Oncol. 2018). At final analysis, APA significantly improved overall survival and time to chemotherapy vs PBO (Small ASCO 2020). We evaluated sexual and urinary function in SPARTAN.

Methods

A total of 1207 pts were randomized 2:1 to APA (240 mg once daily) or PBO. Sexual and urinary function HRQoL was assessed using Functional Assessment of Cancer Therapy-Prostate (FACT-P) response items collected at baseline and Day 1 of: cycle 1 (pre-dose), cycles 2-6, every 2 cycles from 7 to 13, every 4 treatment cycles thereafter, end of treatment, and every 4 months post progression for up to 1 year. Each cycle was 28 d. Descriptive statistics are reported. At each cycle, the number of patients with stable and improved FACT-P scores were summed; mean percentage (range) for APA and PBO were calculated separately.

Results

Median follow-up was 52 mo; median treatment durations were 32.9 mo (APA) and 11.5 mo (PBO). At each cycle, > 90% of all eligible pts completed the questionnaire. Patients receiving APA generally reported stable or improved sexual and urinary function over time during treatment (table). Compared with PBO, a slightly larger proportion of APA-treated patients maintained erectile and urinary functioning compared with baseline or showed improvement over time.

Conclusions

Health-related quality of life data from SPARTAN indicate that baseline sexual and urinary function in pts with nmCRPC is preserved during APA + ADT therapy. Table: 221P

Clinical trial identification

SPARTAN: NCT01946204.

Editorial acknowledgement

William Turner, PhD Parexel International.

Legal entity responsible for the study

Janssen Research and Development.

Funding

Janssen Research and Development.

Disclosure

H. Uemura: Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): FRI-Toyama chem; Honoraria (self), Advisory/Consultancy, Leadership role, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Research grant/Funding (institution): Kyowa-Kirin; Honoraria (self), Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Taiho; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda. S. Oudard: Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Research grant/Funding (self): Ipsen; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Sanofi. B.A. Hadaschik: Honoraria (self), Advisory/Consultancy: ABX; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): German Cancer Aid; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Lightpoint Medical; Honoraria (self), Advisory/Consultancy: Pfizer. F. Saad: Honoraria (self): AbbVie; Honoraria (self): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca / MedImmune; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Sanofi. D. Cella: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Honoraria (self), Research grant/Funding (institution): Astellas; Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Clovis; Officer/Board of Directors: FACIT.org; Honoraria (self), Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Janssen; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Pfizer. E. Basch: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: CareVive Systems; Advisory/Consultancy: Dana-Farber Cancer Institute; Officer/Board of Directors: Journal of the American Medical Association; Advisory/Consultancy: Memorial Sloan Kettering Cancer Center; Advisory/Consultancy: Research Triangle Institute; Advisory/Consultancy: Sivan Healthcare. J.N. Graff: Honoraria (self), Research grant/Funding (institution): Astellas; Honoraria (self), Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Bristol-Myers Squibb; Travel/Accommodation/Expenses: Clovis Oncology; Advisory/Consultancy: Exelixis; Honoraria (self), Research grant/Funding (institution): Janssen; Honoraria (self), Research grant/Funding (institution): Medivation; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme; Licensing/Royalties: Oncoresponse: Exceptional Responders; Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi. S. Dibaj: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. S. Li: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. S.D. Brookman-May: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: JohnsonJohnson. P. De Porre: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: JohnsonJohnson. K. Bevans: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: JohnsonJohnson. J. Trudeau: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. M.R. Smith: Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Research grant/Funding (self): Gilead; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. E.J. Small: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Fortis; Shareholder/Stockholder/Stock options: Harpoon Therapeutics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen; Research grant/Funding (self): Merck Sharp & Dohme. All other authors have declared no conflicts of interest.