ASTRIS is an open-label, single-arm, multinational, real world study of osimertinib for patients with advanced/metastatic epidermal growth factor receptor-mutated (EGFRm) T790M-positive non-small cell lung cancer (NSCLC) who previously received therapy with an EGFR tyrosine kinase inhibitor (EGFR-TKI) (NCT02474355). Data cut-off (DCO) for the second interim analysis was 20 October 2017, with 3014 patients enrolled (full analysis set), including 99 patients in Canada. Adult patients with locally advanced/metastatic EGFRm NSCLC, not amenable to curative surgery/radiotherapy, with confirmation of T790M and prior EGFR-TKI therapy were enrolled. Patients were included with World Health Organization performance status of 0 to 2, as well as those with asymptomatic stable central nervous system (CNS) metastases. Patients received osimertinib 80 mg once daily until loss of clinical benefit. The primary efficacy outcome was overall survival (OS), with secondary outcomes of investigator-assessed response rate (RR), progression-free survival (PFS), and time to treatment discontinuation (TTD). From study start (14 January 2016) to DCO (20 October 2017), 99 patients were enrolled at 12 Canadian centres. Median age was 64 years (30-89 years). Patients were 68% female, 57% Asian, and had ECOG 0/1/2 of 22%/65%/13%. Twenty-five patients had CNS metastases at screening. Gefitinib was the most commonly used previous EGFR-TKI (gefitinib, erlotinib and afatinib were 80%, 14%, and 14%, respectively). Thirty-nine percent had previous chemotherapy; 6% previous immunotherapy; 46% previous radiotherapy. All patients had T790M: 75% tissue, 7% blood and 18% cytology. Biomarker testing methods varied, with the majority (61%) identified by Entrogen EGFR kit. At DCO, 45 patients had discontinued treatment. OS data were immature. Median PFS was 11.0 months (95% CI, 8.9-13.3). Median TTD was 14.9 months (95% CI, 11.2-not calculated). RR was 67.0% (95% CI, 56.7-76.2); sub-analyses showed RR of 69.9% (58.0-80.1), 66.7% (22.3, 95.7) and 55.6% (30.8, 78.5) for patients with T790M by tissue, blood and cytology, respectively. Serious adverse events (AEs) were reported for 18% of patients. AEs leading to dose modifications and discontinuations were reported for 12% and 5% of patients, respectively. The Canadian results from this real world study of osimertinib in advanced/metastatic EGFRm T790M-positive NSCLC, which includes heavily pretreated patients and various approaches to biomarker testing, were comparable to outcomes reported in the phase III study AURA3 (NCT02151981). These findings provide further support for osimertinib as standard of care for EGFRm T790M-positive NSCLC.

BACKGROUNDCombination chemotherapy is associated with improved outcomes in trials of selected fit patients with advanced colorectal cancer (acrc). For older or less-fit patients, combination chemotherapy is associated with greater toxicity and less benefit. Capecitabine monotherapy is a reasonable option for those patients, but the optimal dose remains controversial.METHODSA multicentre phase i/ii trial of reduced-dose capecitabine (2000 mg/m2, days 1-14 every 21 days) was conducted in 221 patients representing one or more of the following subsets: age greater than 65 years (n = 167), Eastern Cooperative Oncology Group (ecog) performance status of 1 or greater (n = 139), elevated lactate dehydrogenase (ldh) (n = 105), or prior pelvic radiation (n = 54). Based on phase i results, patients with prior pelvic radiation received capecitabine 750 mg/m2 twice daily. The goal was to ascertain efficacy in a design that was unlikely to cause high levels of toxicity.RESULTSMedian age in the patient cohort was 72 years. A median of 5 and a mean of 8 capecitabine cycles were given (range: 0-50 cycles). Grade 3 or 4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand-foot syndrome, 7.7% diarrhea). The response rate was 13.6%, with a 69.7% disease control rate. Median progression-free survival (pfs) was 5.6 months. Post progression, 56 patients received further capecitabine monotherapy (median of 4 additional cycles). Median overall survival duration for the patients was 14.3 months. Median survival was significantly higher for those who, at baseline, had an ecog performance status of 0 (compared with 1 or more) and normal ldh (compared with elevated ldh).CONCLUSIONSToxicity is less with dose-reduced capecitabine than with historical full-dose capecitabine, with only a small trade-off in efficacy, seen as a lower objective response rate. The improved tolerability could lead to an increased number of cycles of therapy, and pfs appears to be consistently higher at the lower dose. Those observations should, in the absence of a head-to-head clinical trial, be viewed as compelling evidence that 1000 mg/m2, or even 750 mg/m2, twice daily is an appropriate dose in elderly or frail patients with acrc.

ABSTRACT Aim: Erlotinib is approved for the treatment of patients with metastatic NSCLC following progression of chemotherapy as well for patients who harbour an EGFR mutation. Rash may limit exposure to drug and compromise efficacy. The objective of our study was to determine the proper treatment of EGFR inhibitor-induced rash in the 2nd line or greater setting. A secondary objective was to prospectively observe the relationship between rash and survival and to see if intervention for rash was detrimental. Methods: 150 patients metastatic NSCLC to be started on erlotinib in 2nd/3rd line were randomized to : Arm 1: Prophylactic: Minocycline (150 po bid 4 weeks) on day 1 of erlotinib Arm 2: Reactive: Topical clindamycin plus hydrocortisone +/- minocycline upon rash occurrence Arm 3: Control: No treatment of rash unless severe (Grade 3) Results: Although not statistically significant, previous results showed Arms 1 and 2 had the longest overall survival from randomization. Arm 1: 7.6 months, Arm 2: 8.0 months, Arm 3: 6.0 months p = 0.38 Median survival was analyzed for the 150 patients for worst grade of rash experienced. Survival was significantly longer in patients who experienced severe or moderate rash (Grade 3 or 2) versus mild or no rash (Grade 0/1). Grade 3 rash: 11.4 months, Grade 2 rash: 10.1 months, Grade0/1 rash: 5.5 months p = 0.0093 Porphylactic minocycline in Arm 1 increased Grade 2 and decreased Grade 3 rash significantly. p= 0.3. Number and Percent of Patients with Worst Rash Grade for each Treatment Arm Arm RashGrade 0/1 N% RAsh Grade 2 N% RAsh Grade 3 N% Total 1 25 (50%) 20 (40%) 5 (9.5%) 50 2 28 (46%) 15 (30%) 7 (14.3%) 50 3 28 (46%) 5 (10%) 17 (34.1%) 50 Conclusions: In this prospective trial, a relationship between severity of rash and survival was seen. Moderate (Grade2) and severe (Grade3) rash demonstrated a superior overall survival compared to no or mild (Grade 1) rash. Prophylactic minocycline reduced the incidence of severe Grade 3 rash but increased the moderate Grade2 rash. Prophylactic minocyline should be considered in patients upon initiation of erlotinib therapy. Disclosure: All authors have declared no conflicts of interest.

There is growing evidence that follow-up for patients with early breast cancer (EBC) can be effectively carried out by the primary health care provider if a plan is in place. Here, we present data from a recent survey conducted in Ontario indicating that a shared-care model could work if communication between all health professionals involved in the care of ebc patients were to be improved. Patients and primary care providers benefit when the specialist provides written information about what their roles are and what to expect. Primary care providers need to have easy access to the specialist to discuss areas of concern. Patients also need to share responsibility for their care, ensuring that they attend follow-up visits on a regular basis and that they discuss areas of concern with their primary health care provider. A shared-care model has the potential to provide the best care for the least cost to the health system.

Postmenopausal patients with hormone-sensitive early breast cancer are typically treated with adjuvant endocrine therapy, which significantly reduces the risk of recurrence. Because treatment is of a long duration, side effects From adjuvant therapy can be problematic. The aromatase inhibitors (AIS) are replacing tamoxifen as first-line treatment agents for early breast cancer. Here, we present the side-effect data associated with AIS In relation to bone, gynecologic, and cardiovascular health and to arthralgia and myalgia. Although AIS have been shown to decrease bone density, increase arthralgia, and affect vaginal health, these adverse events are usually manageable, and several strategies can be followed to improve quality of life in women on AI treatment. To optimize adherence to therapy. It is important that these issues are addressed so that women can benefit from treatment.

3577 Background: Combination chemotherapy results in improved outcomes in trials of selected fit patients with ACRC. For older, less fit, more complicated patients, combination chemotherapy is associated with greater toxicity and less benefit. Sequential monotherapy is a reasonable option for these patients. Methods: A multicentre phase I/II trial of capecitabine (Xeloda) 2000mg/m2 d1–14 q21d was conducted in 214 patients in one or more of the following subsets: age≥65 years (167 pts), ECOG performance status ≥1 (139 pts), elevated LDH (105 pts), prior pelvic radiation (54 pts), liver enzyme abnormalities (5 pts). Results: Median age was 72 years (range 38 to 90). At a median follow-up of 7.2 months, 131 patients are alive. A median 4 and mean 6.5 cycles were given (range 1 to 33). Prior pelvic radiation required dose reduction to 1500mg/m2 for diarrhea in the 3rd cycle. Of 192 patients evaluable for toxicity, there were no grade 3/4 hematologic toxicities. Grade 3/4 toxicity occurred in 22% of patients d...

3764 Background: Capecitabine [Xeloda (XEL)] is an oral pro-drug of 5-fluorouracil, which in turn forms a terniary complex with thymidylate synthase and reduced folate. Folate metabolism could therefore have an impact on the clinical efficacy of XEL. Players include homocysteine, which is converted to methionine in a reaction forming tetrahydrofolate in the presence of vit B12. These and other factors may play a prognostic role in pts with ACRC. Methods: A multicentre phase I/II trial of XEL 2000mg/m2 d1–14 q21d was conducted in 139 pts in one or more of the following subsets: age > 65 years (99 pts), ECOG performance status (PS) >1 (85 pts), LDH (43 pts), prior pelvic radiation (36 pts), liver enzyme abnormalities (4 pts). A substudy is reported on the prognostic significance of serum and RBC folate, vit B12, homocysteine, LDH, LDH isoenzymes, and ECOG PS. Results: 86 pts were evaluable for homocysteine levels, 122 for LDH, and 137 for ECOG PS. High homocysteine (n=37) predicted for markedly shorter median overall survival (MS) vs normal levels (n=49). Serum folate, RBC folate, and vit B12 did not predict for survival, though high folate predicted for tumour response. High LDH (n=71) predicted for shorter MS vs normal LDH (n=51), and lower response rate. Pts with high LDH have a lower proportion of LDH isoenzyme 1 (15.1%) vs pts with normal LDH (21.5%), p<0.0001. Less LDH isoenzyme 1 depression predicted for better MS (p=0.08). ECOG PS 0 (n=52) had worse MS vs ECOG PS 1 to 2 (n=85). Pts with normal LDH and high homocysteine had a poor MS (9.4 mos), suggesting homocysteine is a more powerful prognostic factor. Conclusions: High serum homocysteine, high LDH and poor PS are poor prognostic factors in pts with ACRC treated with XEL. Accrual continues and updated results including multivariate analysis will be presented. Supported by Hoffman-La Roche Canada. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-LaRoche Canada