Rogers, Jane E.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 (online only) for more. PURPOSE To provide guidance on the recommended management of cancer in pregnant patients. METHODS A multidisciplinary Expert Panel convened and conducted a systematic review of the literature. RESULTS The systematic review identified 450 eligible studies. Much of the evidence consisted of observational data, case series, and case reports. RECOMMENDATIONS Management of cancer during pregnancy should be grounded in a values-based informed-consent process outlining maternal and fetal risks and anticipated benefits. Diagnostic evaluation should follow the as low as reasonably achievable (ALARA) principle, with timing of diagnostic studies individualized based on urgency of cancer detection, potential dangers of delay, and the balance of risks to both the pregnant patient and her embryo or fetus. Due to significant risk of harm to the developing embryo and/or fetus, systemic therapy should be deferred until the second trimester. Methotrexate, hormonal therapies, human epidermal growth factor receptor 2–targeted agents, vascular endothelial growth factor and poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and all cellular therapies are contraindicated during pregnancy, regardless of gestational age. For patients who wish to continue their pregnancy, delivery should be planned at or after 37 weeks, with the final chemotherapy dose scheduled 2-4 weeks before birth. Referral to psychosocial support services is essential to address emotional and practical challenges, reduce distress, and support shared decision making. Additional information is available at www.asco.org/survivorship-guidelines .

e15055 Background: An increasing number of pt and tumor c have predictive and prognostic implications in mCRC. However, there is no consensus on their reporting in trial results. Methods: Pt c and SF from 136 phase III trials of systemic therapies (Rx) in mCRC published between 1988 and 2018 (68,326 pts) were collected. Trials were also grouped per publication date (G1: 1988-97; G2: 98 – 2007; G3: 08-18). Patterns of reporting and trends across G were evaluated. Results: Pt c consistently reported were performance status, PS (98.5%), age (92.6%) and gender (90.4%); race (20.6%) & weight/BMI/BSA were not (13.2%). Tumor c frequently reported were metastatic (met) spread (70.6%) while time intervals related to disease course (25%) and synchronous met vs not (19.1%) were omitted. Of note, primary site was largely reported as colon vs rectum (69%) and sidedness or anatomical location was discernable only in 10.3%. Prior Rx reporting focused on chemo (58.5%) with radiation and surgery and reported in 34% & 28.7%. Reporting of prognostic factors was variable and limited: histology grade CEA, alk phos, LDH (range 10.3-15.4%). Only 11.8% of trials reported genomic factors - KRAS MT was included in all with BRAF MT in 4.4%. Of 140 trials used for SF analysis, 115 had ≥ 1 (range 1-7). Common SF were PS (60%), geography /institution (55.7%). Prior Rx (27%), met spread (24.3%) were sometimes used while primary site (7.8%), genomic factors (6.1%) rarely were. Trends across G are per Table. Conclusions: There is marked inconsistency in pt c & SF reporting in mCRC trials. Consensus guidelines will aid in standardization of trial interpretation and future meta-analyses; and will need to be updated based on emerging data. [Table: see text]

656 Background: Despite multiple trials of new agents in metastatic colorectal cancer (mCRC), long term outcomes remain poor. This study explores the changing trends in the design, interpretation and outcomes of phase III randomized controlled trials (RCT) in mCRC over time. Methods: Phase III RCTs of systemic therapy for mCRC with enrollment between 1986 and 2016 were identified through 4 electronic databases and grouped into 3 time periods (1986-1996 – T1; 1997-2006 – T2 & 2007-2016 – T3). Study selection, quality appraisal and data collection were performed by 2 independent investigators. Study characteristics, primary and secondary endpoints, and authors’ interpretation of results and conclusions were analyzed. Improvement in overall survival (OS) was the difference between experimental and control arms. A study was deemed positive if it met its end point, was recommended for further study or for adoption for clinical use (p ≤ 0.05 significant for all analyses). Results: One hundred fifty trials (T1=36, T2=62, T3=52) with 77494 patients (T1=12406, T2=39158, T3=25930) were included. Although 1st line therapy trials continued to be the most common across all T, the percentage (%) of trials evaluating 3rd line and beyond (T1=0, T2=3, T3=27) have increased significantly over time as have trials with targeted agents (T1=11, T2=34, T3=79). Although OS remains the most common primary end point, more trials in T2 & T3 have used progression-free survival instead (14 vs 47 & 44). The % of trials with negative results but interpreted as positive increased over time (T1=18; T2=42; T3=35). Across all T, the median improvement in OS (months, m) of these trials was significantly lower compared to the trials that met primary end point across all T (T1 = 0 vs 1.8 m, T2 = -0.1 vs 3.25, T3 = -0.25 vs 2.55). Conclusions: A significant shift has occurred over the past three decades in the design and interpretation of phase III trials in advanced CRC. Any interpretations of potential survival benefits from trials that have not met primary end point must be made with significant caution.

678 Background: Improvements in outcome of medical therapy for mCRC are closely linked to availability of active agents. Based on phase III clinical data, regorafenib, a multikinase inhibitor, received FDA approval September 2012 for patients with mCRC previously treated with all approved therapies. Post regorafenib therapy (PRTx) has not been established. Based on clinical observations, we established a multi-institution collaboration to assess chemotherapy response in mCRC after regorafenib therapy. Methods: After IRB approval, patient records at Mayo Clinic (MC), MD Anderson (MDA) and the University of Southern California (USC) from April 2010 to February 2014 were reviewed for regorafenib use and outcomes for mCRC. Therapies, patient and tumor characteristics were reviewed. Response and progression were determined by investigator review. Kaplan-Meier method was used to calculate survival. Results: Regorafenib was given to 173 patients with mCRC (MC:59 MDA:95 and USC:19). Of these, 11 (6%) continued on regorafenib at time of analysis and 98 (57%) received no additional therapy. PRTx was given to 64 (37%) patients, 31 of which went on a clinic trial. 33 patients were treated with standard approved therapy of which 11 (33%) progressed, 20 (61%) showed response or SD, and 2 (6%) were not evaluable. Out of the 33 treated with standard agents, 8 (24%) had stable disease or response to a treatment previously discontinued without definitive PD, whereas 4 (12%) responded to rechallenge with chemotherapy previously discontinued due to PD. Response was noted in 8 (24%) patients that received an agent not given prior to regorafenib. After discontinuation of regorafenib, mOS was 6.5 mo (CI 4.9 – 9.4), and the probability of survival at 6 and 12 months was 52% and 27% respectively. Conclusions: With the caveat of a small sample size and a potential selection bias, our multi-institution study shows that re-utilizing standard treatment options after regorafenib may be beneficial in select patients with mCRC including in patients with progression on identical therapy before regorafenib. Further retrospective and prospective studies could be warranted to define the role of regorafenib as a chemotherapy re-sensitizing agent.