tbuckley/cabot-search huggingface dataset:
Outcomes of melanoma soft parts/clear cell sarcoma (MSP/CCS) patients (pts) with immune and targeted therapies.
Authors: Amy Little Jones, Aron Joon, Lauren Elaine Haydu, Alexander J. Lazar, Michael T. Tetzlaff, Vinod Ravi, Michael A. Davies
Journal: Journal of Clinical Oncology (2019)

e21046 Background: Overall survival (OS) for pts with cutaneous melanoma has vastly improved with checkpoint inhibitors (CPI) and targeted therapy (TT), but less is known about outcomes of other rare tumors showing melanocytic differentiation. We examined outcomes for metastatic pts with MSP/CCS at MD Anderson (MDA) to characterize outcomes with contemporary therapies. Methods: Pts with MSP/CCS were identified in the MDA databases. Pts with &lt; 2 visits to MDA or without molecular confirmation of dx were excluded. Log-rank testing was used to compare OS among distributions. Results: A total of 102 MSP/CCS pts were identified. Initial diagnosis was local disease 46%, regional metastases 34%, and systemic metastases 20%. Primary tumor site was lower extremity (LE) 48%, GI tract 29%, upper extremity (UE) 18%. 65 pts were diagnosed with metastatic disease (dz), including 32% with lung-only, 14% liver-only, and 51% with multiple metastatic sites. Median OS from diagnosis of distant metastatic dz was 22 mos (95% CI 16-34 mos). Primary tumor site (GI 46.4 vs. LE 19.1 vs. UE 14.7 mos; p = 0.018) and race (white 26.8 vs. black 6.5 mos, p = 0.019, HR 0.45) were significantly associated with OS from distant metastasis; sex, age, decade of diagnosis, size of primary, and prior treatment with neoadjuvant or adjuvant therapy were not. Treatments for metastatic dz included chemotherapy (n = 29), biochemotherapy (n = 11), biotherapy (n = 5), CPI (n = 11) and TT (n = 19). Median OS was 15.9 mos from start of CPI (range 10.7 to NR) and 16.9 mos from start of TT (range 7.8 to NR). Median OS from metastatic dz for pts not treated with CPI or TT was 17.1 mos (range 12.4 to 32.5), which was not significantly different versus CPI or TT. Duration of response was &lt; 6 mos for 91% pts receiving CPI and 89% pts receiving TT. One pt had a durable response (41.8 mos) to anti-PD1 and one pt had a durable response (24.8 mos) to an AKT inhibitor. Conclusions: While rare responses to CPI and TT were observed, no significant difference was detected in OS compared to traditional therapies in pts with metastatic MSP/CCS. The development of more effective therapies remains an unmet need for this disease.
Effect of exercise during adjuvant chemotherapy for breast cancer.
Authors: Barbara K Haas, Cynthia R. C. Osborne, Svetislava J. Vukelja, Jennifer Selman, Trevor Davis, Gary T. Kimmel
Journal: Journal of Clinical Oncology (2019)

6524 Background: In 2018, an estimated 266,120 women faced the challenge of living with breast cancer and approximately 40,920 died from their disease. Nearly 100% of these women experienced significant treatment related side effects that negatively impact quality of life (QOL). Exercise has repeatedly demonstrated to alleviate many of the side effects, improve QOL, and decrease cancer recurrence and mortality. In spite of this evidence, women do not maintain exercise during treatment for breast cancer. The purpose of this randomized controlled trial was to determine the effectiveness of exercising the day chemotherapy is administered on 1) the persistence with an exercise program, 2) side effects, and 3) QOL. Methods: Eligible women were randomly assigned to a control or experimental group. As part of their treatment plan, all participants were referred to one of 14 community-based exercise centers to exercise. Experimental group also exercised at one of two cancer centers each day chemotherapy was administered. Outcome measures include exercise retention and chemotherapy, completion; cancer-related fatigue, nausea/vomiting, peripheral neuropathy, weight gain, and QOL. Outcome measures were assessed prior to every second course of chemotherapy and 3- and 6-months post-chemotherapy. Results: 273 women with Stage I-III breast cancer receiving chemotherapy were enrolled in the study. The number of participants who withdrew from exercise was higher among those in the control group (n= 16; 12.4%) compared with those in the experimental group (n = 10; 6.9%). At cycle 5, those in the experimental group reported less motor peripheral neuropathy than those in the control group (p = .018) and higher physical well-being scores than those in the control group (p = .047). Conclusions: The highest impact of the intervention was on attrition from exercise. Since participants in both the control and experimental groups exercised throughout chemotherapy, it is not surprising that the groups performed comparably with regard to side effects and QOL. Given the positive effects exercise has demonstrated on persons receiving cancer treatment in numerous studies, having patients exercise in the cancer center on the day of chemotherapy is a significant step toward engaging persons receiving chemotherapy in an exercise program.
Utilization and reach of the Fight Colorectal Cancer Late Stage MSS CRC Clinical Trial Finder.
Authors: Reese Garcia, Andrea Dwyer, Sharyn Worrall, Christopher Ryan Heery, Dustin A. Deming, Al Bowen Benson, Anjee Davis
Journal: Journal of Clinical Oncology (2019)

3561 Background: Colorectal cancer (CRC) remains one of the most lethal cancer killers worldwide. Recently, research has shown great strides in the treatment of MSI-H mCRC using immunotherapy, however, these treatments have not been effective in MSS patients, who make up a majority of CRC cases. Due to numerous barriers, clinical trial enrollment numbers remain as low as 9% of the eligible populations, despite the reliance of many late stage CRC patients on clinical trials for treatment. Perhaps greatest of these barriers is the lack of meaningful patient-facing clinical trial matching, making advances in MSS mCRC IO clinical research extremely slow. Methods: In May 2017, Fight Colorectal Cancer (FightCRC) launched its web-based trial finder, The Late Stage MSS Trial Finder (TF) with the late Dr. Tom Marsilije, a stage IV CRC patient and researcher, and Flatiron Health. The TF is a publicly available immunotherapy-based repository of clinical trials. An algorithm automatically codes for a subset of trials from ClinicalTrials.gov to be uploaded into the tool, and trained FightCRC advocates follow a strategic logic flow to prioritize trials of highest potential benefit and lowest risk for patients. Results: Between 30 and 100 trials are uploaded into the TF for curation each week. A total of 378 trials have been indexed in the TF to date. In February 2019, a mobile application was introduced. From May 2017 to January 2019, the tool has seen &gt; 15,000 users, yielding 26,000 searches in 105 countries; primarily from the United States, China, the United Kingdom, Canada, and France. On average, users navigate to 2.5 pages and spend &gt; 2.5 minutes per use. Providers are using this as a tool to find clinical trials and to discuss these options in real time. CRC patient feedback confirmed the platform functionality. Conclusions: The Trial Finder is a unique tool for MSS mCRC patients pursuing clinical trials. The success of the tool may be attributed to patient focused selection of therapies that show promise. The FightCRC late stage MSS CRC trial finder is being widely utilized, in diverse settings. With our patient curators and Medical Advisory Board, FightCRC will improve the search features and outcome tracking with user feedback. The goal for the TF is to address key barriers to patient entry into clinical trials and promote patient-provider discussions to inform decision making.
HER2 cluster amplification as a factor of an especial sensitivity for anti-HER2 neoadjuvant therapy with biosimilar of trastuzumab in Russian women with breast cancer stage II-III.
Authors: Irina Vladimirovna Kolyadina, Olga Gordeeva, Inna Ganshina, Larisa Zavalishina, Yulia Andreeva, Georgy Frank, Nikita Savelov, Elena Tuzova, Lyudmila Zhukova, Yana Vishnevskaya, Aleksandr Arkhipov, Vahan Yurikovich Bokhian, Dmitry Komov, Irina Poddubnaya
Journal: Journal of Clinical Oncology (2019)

e12102 Background: Effect of neoadjuvant chemotherapy (NACT) is extremely important for patients with HER2-positive breast cancer stage II-III as it correlates with long-term outcomes. However, predictive factors for achieving complete pathologic response (pCR) remain unclear. Aim of the study: Assess an impact of clinical, morphological and genetic factors on pCR achievement in patients with HER2-positive breast cancer stage II-III treated by biosimilar of trastuzumab. Methods: We studied treatment results in 73 patients with HER2-positive breast cancer (BC) stage II-III (aged 29-71, median – 51 years), treated with NACT with anti-HER2 therapy and radical surgery in “N.N. Blokhin National Medical Research Center of Oncology” оf the Ministry of Health of the Russian Federation in 2015-2018. After radical surgery pathologic response was assessed. Initially operable tumors were observed in 45,2% patients, locally advanced - in 53,4%. Luminal HER2-positive BC was diagnosed in 41,1%, non-luminal HER2-positive in 58,9%. Ki67 was high (≥ 20%) in 91,5%. NACT included anthracycline and non-antracycline regimens with addition of biosimilar of trastuzumab ± pertuzumab. Radical mastectomy was performed in 78,8% patients, 21,2% had breast-conserving surgery. We studied biopsies obtained before the start of treatment in all women, HER2 amplification was detected by HER2 IQFISH pharmDx (DAKO) kit in accordance with ASCO/CAP 2018 guidelines. In 87,1% HER2+ status was defined as ASCO/CAP 2018 category 1; cluster amplification was detected in 30,1% patients. We analyzed the rate of bpCR и tpCR achievement depending on clinical, pathological data and amplification of HER2. Results: Pathologic complete response in primary tumor (bpCR) was achieved in 57,4%, both in primary tumor and lymph nodes (tpCR) – in 48,9% patients; bpCR achievement depended on age, NACT regimen, addition of pertuzumab and HER2 copy number ( &lt; 0,05). The highest rate of bpCR was noted in women aged 50 and older (71,9%, p = 0,026); in patients received TCH±Р regimen (80,0%, p = 0,045); with addition of pertuzumab (88,9%, p = 0,049); and if cluster amplification was detected (81%, p = 0,013). Cluster amplification was the only one significant predictive factor for achieving tpCR: with cluster amplification - 68,8%, without - 38,7% (p = 0,049). Conclusions: Cluster amplification of HER2 is the most significant factor of especial sensitivity for NACT with biosimilar of trastuzumab in HER2-positive BC stage II-III.
Phase 1 dose escalation study of XMT-1536, a novel NaPi2b-targeting antibody-drug conjugate (ADC), in patients (pts) with solid tumors likely to express NaPi2b.
Authors: Anthony W. Tolcher, Susanna Varkey Ulahannan, Kyriakos P. Papadopoulos, William Jeffery Edenfield, Ursula A. Matulonis, Timothy F. Burns, Rebecca Mosher, Barbara Fielman, Eric Hailman, Howard A. Burris, Kathleen N. Moore, Erika Paige Hamilton
Journal: Journal of Clinical Oncology (2019)

3010 Background: XMT-1536 is a Dolaflexin ADC targeting the sodium-phosphate cotransporter NaPi2b, expressed in ovarian, non-squamous lung, papillary thyroid, endometrial, papillary renal and salivary duct cancers. Methods: In this ongoing Phase 1 study, pts with solid tumors likely to express NaPi2b, who progressed on standard therapy, are treated with intravenous XMT-1536 using a 3+3 design with a modified Fibonacci escalation. NaPi2b expression by IHC is being examined retrospectively in archived tumors. Primary objectives in dose escalation are safety and tolerability and determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). (ClinicalTrials.gov NCT03319628). Results: As of Jan. 28, 2019, 36 pts (22 ovarian, 7 endometrial, 4 NSCLC, 3 other) have received treatment with XMT-1536. Treatment was initially given every 3 weeks (q3w); 20 pts were treated in dose cohorts from 3 to 40 mg/m 2 . There was one DLT of reversible AST elevation at 40 mg/m 2 . The dosing interval was then changed to every 4 weeks (q4w), and dose escalation was restarted at 20 mg/m 2 . There was one DLT of reversible AST elevation at 30 mg/m 2 on the q4w schedule. Further followup and dose escalation are ongoing. The most common (≥10% of patients) treatment-related adverse events (TRAEs) have been nausea, fatigue, headache, increased AST, anorexia, increased alkaline phosphatase, fever, increased GGT, myalgia, and vomiting. Grade 3 TRAEs were reversible AST increases in 3 patients and increased GGT, decreased lymphocytes, and systolic congestive heart failure in 1 patient each. Treatment-related serious AEs of fever and systolic congestive heart failure occurred in 1 patient each. Among patients dosed at 20 mg/m 2 or higher who had restaging scans (n=20), there were 2 PR, in ovarian cancer pts at 30 mg/m 2 q3w and 20 mg/m 2 q4w, and 11 SD, with disease control maintained for up to 24 weeks. Patient-level results for NaPi2b expression will be presented. The systemic exposure of total payload showed approximately dose-proportional increase. Plasma concentration of free drug payload and its active metabolite were low. Conclusions: XMT-1536 has been well-tolerated up to the 30 mg/m 2 dose level with early signs of anti-tumor activity. Dose escalation continues in pts with advanced solid tumors likely to express NaPi2b. Clinical trial information: NCT03319628.
The ESCAPADE Study: Early supportive care for advanced cancer patients, assessing care delivery and provider engagement.
Authors: Oren Hannun Levine, Daryl Bainbridge, Gregory Russell Pond, Marissa Slaven, Sukhbinder K. Dhesy-Thind, Jonathan Sussman, Ralph M. Meyer
Journal: Journal of Clinical Oncology (2019)

e23142 Background: Advanced cancer patients benefit from early integration of palliative care (EIPC) with usual care. A proposed model of EIPC reserves specialized palliative care (SPC) for complex patients, while primary care providers (PCP) and oncologists oversee basic palliative care (PC). We studied the attitudes among patients and their healthcare providers regarding delivery of EIPC. Methods: A cross-sectional study at a tertiary cancer centre in Ontario. Patients with newly diagnosed incurable gastrointestinal (GI) cancer were surveyed using a study specific instrument for the outcomes of interest: importance of and preferences for accessing support across 8 domains of PC (disease management, physical, psychological, social, spiritual, practical, end of life care, loss and grief). Healthcare providers within the circle of care completed a parallel survey for each recruited patient. Primary analysis involved use of descriptive statistics to summarize survey results and concordance between patient and provider responses. Results: From Oct 2017 - Nov 2018, 67 patients were surveyed (median age 69, 34% female). 90% had an identified medical oncologist, and 19% had SPC. 97% had a PCP, but only 42% listed a PCP as part of the care team. Median time from first oncology assessment for advanced cancer to patient survey completion was 52.5 days. 85 providers responded (oncologist = 59, PCP = 20, SPC = 6; response rate 92%; 1-3 physician responses per patient). Disease management and physical concerns were most important to patients. In these domains, 67% and 81% of patients endorsed receiving care from the preferred provider, but concordance between patient and physician responses regarding most responsible provider was only 58% and 38%. For all other domains, 87 – 100% of patients attributed primary responsibility to self or family rather than any healthcare provider. Conclusions: Respondents did not assign responsibility to physicians early in the disease trajectory for many domains of PC. Our findings suggest that incorporating patient activation and empowerment into EIPC requires further study. PCPs appeared to have limited involvement in PC for newly diagnosed advanced GI cancer patients.
Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial.
Authors: Richard T. Penson, Ricardo Villalobos Valencia, David Cibula, Nicoletta Colombo, Charles A. Leath, Mariusz Bidziński, Jae-Weon Kim, Joo-Hyun Nam, Radoslaw Madry, Carlos Hernández Hernández, Paulo Alexandre Ribeiro Mora, Sang Young Ryu, Tsveta Milenkova, Elizabeth S. Lowe, Laura Barker, Giovanni Scambia
Journal: Journal of Clinical Oncology (2019)

5506 Background: Data from a randomized Phase II trial (NCT00628251) of olaparib (capsules, 200 or 400 mg bid, n=32 per arm) vs pegylated liposomal doxorubicin (PLD, n=33) in gBRCAm OC pts with recurrence ≤12 months after prior platinum therapy indicated efficacy for olaparib (Kaye et al. JCO 2012). However, the efficacy of PLD was higher than previously reported in this setting. We led a confirmatory Phase III, open-label study of olaparib vs non-platinum chemotherapy in gBRCAm PSR OC pts (NCT02282020). Methods: Pts were randomized (2:1) to olaparib tablets (300 mg bid) or chemotherapy treatment of physician’s choice (TPC) (paclitaxel [P; 80 mg/m 2 on day 1 (D1), D8, D15, D22 every 4 weeks (q4w)], topotecan [T; 4 mg/m 2 D1, D8, D15 q4w], gemcitabine [G; 1000 mg/m 2 D1, D8, D15 q4w] or PLD [50 mg/m 2 D1 q4w]) until progression, stratified by: TPC, prior lines of chemotherapy (2–3 vs ≥4) and platinum-free interval (6–12 vs &gt;12 months). Primary endpoint: ORR (blinded independent central review [BICR]). Secondary endpoints included PFS and safety. Results: 266 gBRCAm PSR OC pts were randomized (olaparib, n=178; TPC, n=88 [ PLD, n=47; P, n=20; G, n=13; T, n=8]); 12 in the TPC arm withdrew before receiving study treatment. 223 pts (84%) had baseline BICR measurable disease (olaparib, n=151; TPC, n=72). ORR was 72% with olaparib vs 51% with TPC (OR 2.53, 95% CI 1.40–4.58; P=0.002). HR for PFS by BICR was 0.62 (95% CI 0.43–0.91; P=0.013; median 13.4 vs 9.2 months [olaparib vs TPC]) and by investigator assessment was 0.49 (95% CI 0.35–0.70; P&lt;0.001; median 13.2 vs 8.5 months, respectively). Most common adverse events (AEs) with olaparib were nausea (65% vs 34% [TPC]) and anemia (50% vs 25%) and with TPC were palmar-plantar erythrodysesthesia (PPE; 36% vs 1% [olaparib]) and nausea. Most common grade ≥3 AEs in either arm were anemia (21% [olaparib] vs 0 [TPC]), PPE (0 vs 12%) and neutropenia (6% vs 11%). For olaparib vs TPC, serious AEs were reported by 24% vs 18% and AEs led to treatment discontinuation in 7% vs 20%. Conclusions: Pts with gBRCAm PSR OC receiving olaparib monotherapy had a significant, clinically relevant improvement in ORR and PFS vs TPC, with no new safety signals. Clinical trial information: NCT02282020.
Clinical outcomes in patients with melanoma brain metastases at a tertiary cancer center.
Authors: William J Phillips, Bryan Lo, Michael Ong, Tyler Smith, Xinni Song
Journal: Journal of Clinical Oncology (2019)

e13586 Background: Brain metastases are observed in more than 40% of all patients with stage IV melanoma. In recent years, more extensive use of stereotactic radiation (STRT) and the advent of immune checkpoint inhibitors and BRAF targeted therapies have positively impacted outcomes in patients with metastatic melanoma (MBM) In this study, we examined real-world clinical outcomes of patients presented with melanoma brain metastases (MBM). Methods: This retrospective review evaluated MBM patients treated at the Ottawa Hospital. Clinical, radiologic, and pathologic variables were collected from the electronic medical records from January 2000 to June 2018. Results: A total of 277 patients fulfilled the inclusion criteria. Median overall survival was 4 months. LDH was the only significant prognostic factor in this study. Over 65% of brain metastases were detected due to the presence of neurological symptoms, while surveillance and restaging identified asymptomatic brain metastases in the remaining patients. Detection by neurological symptoms was related to larger (p &lt; 0.001) and haemorrhagic (p = 0.032) intra-cranial lesions as well as decreased overall survival (HR = 1.2, p = 0.018). With regards to locoregional treatment STRT radiation outperformed WBRT alone in patients with single and oligo (2-6 lesions) brain lesions (HR = 0.149, p = 0.001 for oligo; HR = 0.149, p = 0.003 for single) and was associated with approximately a 3-fold increase in median survival. STRT was used 2-fold less frequently in patients with more than one lesion (54.8% in single; 31.7% in oligo). In patients receiving systemic therapy, immunotherapy is the only modality demonstrated overall survival benefit compared to no systemic treatment (HR = 0.511, p = 0.014). Furthermore, patients receiving STRT in combination with immunotherapy outperformed patients receiving STRT with WBRT (HR = 0.389, p = 0.009). Conclusions: Results from this study support the consideration of routine screening of high-risk asymptomatic patients, the increased use of STRT in patients with multiple intra-cranial lesions. The efficacy of immunotherapy in patients with MBM is consistent with current clinical trial data.
Factors associated with osteonecrosis of the jaw in women with breast cancer receiving high-dose bisphosphonates to prevent breast cancer metastases as part of the SWOG 0307 trial.
Authors: Darya Kizub, Jieling Miao, Mark M. Schubert, Alexander H. G. Paterson, Mark J. Clemons, Elizabeth Claire Dees, James N. Ingle, Carla Isadora Falkson, William E. Barlow, Gabriel N. Hortobagyi, Julie Gralow
Journal: Journal of Clinical Oncology (2019)

552 Background: Bisphosphonates reduce the risk of bone metastases in postmenopausal women with early-stage breast cancer but carry the risk of osteonecrosis of the jaw (ONJ). We used the data collected in the S0307 trial to describe factors associated with provoked and unprovoked ONJ. Methods: In S0307, 6097 patients with Stage I-III breast cancer who had surgery were randomized to receive zoledronic acid (ZA) 4mg IV monthly for 6 months, then every 3 months, clodronate (CL) 1600mg daily, or ibandronate (IB) 50mg daily for three years, with no difference in bone metastases or disease-free survival. Patients completed dental procedures prior to and had a dental exam at enrollment. Pearson’s Chi-squared and Student’s T-test were used to test differences in categorical and continuous variables, respectively; logistic regression was used test independent association. Results: Of 5836 evaluable women, 48 developed ONJ, which was associated with bisphosphonate type (28/2124 (1.26%) for ZA, 8/2185 (0.36%) for CL and 12/1527 (0.77%) for IB (p = 0.002). Median time to onset of ONJ was 24.9 (1.4-66.6) for ZA, 41.2 months (range 33.8-67.4) for CL, 23.9 (2.1-75.3) for IB (p = 0.0447). Infection was present in 21 (43.8%) and absent in 20. ONJ was considered unprovoked in 20 (41.7%) and provoked by dental extraction in 20 (41.7%), periodontal disease in 14 (29.2%), denture trauma in 6 (12.5%), other dental surgery in 3 (6.3%). ONJ was associated with dental calculus (OR 2.03 (95% CI: 1.08-3.81), gingivitis (OR 2.11, 95% CI: 1.12-3.98), and periodontal disease (OR 2.87, 95% CI 1.45-5.53) that were moderate/severe and &gt; 4mm periodontitis (OR 2.20, 95% CI 1.18-4.08). Patients with provoked and unprovoked ONJ had similar amounts of dental disease and lesion location. ONJ was not associated with dentures, plaque, chemotherapy, corticosteroids or renal adverse events. In multivariate analysis (limited by small sample), only bisphosphonate type was associated with ONJ. Conclusions: ONJ prevalence was low, likely due to patients completing dental procedures before enrollment. ZA carried a higher risk of ONJ (though current adjuvant dosing interval recommendations are less frequent), with time to onset similar to IB. Oral CL and IB (not currently available in the United States) are thus likely more appropriate for patients with poor dental health. Clinical trial information: NCT00127205.