- Email: [email protected]
The impact of percentage of time on chemotherapy on survival in recurrent ovarian cancer
Abstracts / Gynecologic Oncology 141 (2016) 2–208
Similarly, high-grade disease was driven by HPV16/18 in AAW with normal cytology and abnormal cytology (≥ASCUS). Likewise, looking at age deciles (from 21–59 years), the absolute risk of CIN3+ is always higher with HPV16/18 versus the 12 other hrHPV types for AAW irrespective of age (nonsignificant for N50 years because of the small number of cases) Conclusions: The ATHENA trial, the largest cervical cancer screening study to date in the United States, indicates that most cases of highrisk cervical disease are caused by HPV16/18. This is in spite of reports indicating an HPV genotype distribution difference in AAW and non-Hispanic Caucasian women and its impact on disease prevention with currently available HPV vaccines. This is similar to what has been documented in non-Hispanic Caucasian women. Therefore, this calls into question the clinical relevance of creating race-specific HPV vaccines.
gynecologic cancer surgery, namely uterine and ovarian cancer, and may aid in preoperative counseling. Table 1 Preoperative Risk Factors Included in the mFI.
OF
146
doi:10.1016/j.ygyno.2016.04.380
doi:10.1016/j.ygyno.2016.04.381
350 – Poster The impact of percentage of time on chemotherapy on survival in recurrent ovarian cancer T. Febbraroa,b, A. Puglisib, Y. Zhoub, J.A. Hurteaub, C.V. Kirschnerb, G.C. Rodriguezb, K.T. Wardc, E.D. Mooreb. aThe University of Chicago Medicine, Chicago, IL, USA, bNorthshore University Health System, Evanston, IL, USA, cPresence Saint Francis Hospital, Evanston, IL, USA
Objectives: We sought to determine if the modified frailty index (mFI) correlates with morbidity and mortality in patients undergoing gynecologic cancer surgery. Predicting outcomes is important in preoperative counseling and surgical planning. The concept of frailty is emerging as a potential tool for predicting worse surgical outcomes. It is defined as an increase in one’s vulnerability for developing dependency or death because of a loss of physical or mental reserve, often in the absence of a defined comorbidity. Methods: Patients who underwent gynecologic cancer surgery from 2006 to 2012 in the National Surgical Quality Improvement Program (NSQIP) database were analyzed. mFI was calculated using 11 preoperative variables. (See Table 1.) Associations between mFI and readmission, major complications, and 30-day mortality were assessed. A multiviariable logistic regression model was used to predict adverse outcomes, after adjusting for age, race, and body mass index. Results: A total of 13,093 patients who had surgery for a gynecologic malignancy were identified (6,728 [51.4%] with uterine, 2,765 [21.1%] with ovarian, 2,373 [18.1%] with cervical, and 1,227 [9.4%] with other gynecologic cancers). For all gynecologic malignancies, there were 654 (5.0%) readmissions, 890 (6.8%) patients with 1 or more major complications, and 93 (0.008%) deaths within 30 days. When including all women who underwent gynecologic cancer surgery, increasing mFI was significantly associated with increased risk for major complications (OR 1.19, 95% CI 1.09–1.30, P b .001) and 30-day mortality (OR 1.49, 95% CI 1.18–1.87, P = .001), but not for readmission. For example, 30-day mortality increased from 0.4% in patients with an mFI of 0, to 7.6% in those with an mFI of 0.3 or higher. When analyzing each malignancy individually, this trend was noted in both uterine and ovarian cancer patients, both younger and older than 65 years of age. For example, 30-day mortality increased from 0.4% in uterine cancer patients with an mFI of 0, to 5.7% in those with an mFI of 0.3 or higher, and from 0.8% to 12.5% in ovarian cancer patients. There was no trend found for cervical or other gynecologic cancer patients. Conclusions: The mFI can be calculated with routinely collected clinical data and is predictive of adverse outcomes in patients undergoing
Objectives: Most women with ovarian cancer achieve remission after first-line chemotherapy. However, the majority will experience recurrence, and many women will receive additional palliative chemotherapy yet eventually succumb to their disease. With the benefit of additional palliative chemotherapy debatable, balancing quality of life with chemotherapy toxicity is of paramount importance. This study aims to determine whether additional time receivng salvage chemotherapy leads to improved overall survival (OS) in those with recurrent ovarian cancer. Methods: A single institutional cancer registry was queried to identify women treated for recurrent ovarian cancer from 2004 to 2014. A retrospective chart review was performed to abstract clinical data on a randomly selected sample of 100 women. Patients were divided into tertiles based on percentage of time receiving chemotherapy from recurrence to death with the first tertile having the smallest percentage of time on chemotherapy and the third tertile having the greatest percentage of time on chemotherapy. KaplanMeier and the log-rank tests were used to compare survival between groups. Results: Among all recurrent ovarian cancer patients, a greater percentage of time on chemotherapy from recurrence to death was associated with poorer OS (first tertile 44 months vs third tertile 31 months, P = .02). In those that became platinum resistant, a greater percentage of time of chemotherapy was associated with poorer OS whereas in platinum-sensitive women a greater percentage of time on chemotherapy did not improve OS (platinum resistant: first tertile 47 months vs third tertile 31 months, P = .003; platinum sensitive: first tertile 42 months vs third tertile 53 months, P = .31). In platinum-resistant women, a greater percentage of time on chemotherapy from platinum resistance to death also did not improve OS (first tertile 39 months vs third tertile 34 months, P = .23). Conclusions: In this cohort of recurrent ovarian cancer patients, a greater percentage of time on chemotherapy did not lead to improved survival, and in some cases, worsened survival. In a palliative setting, caution should be taken against overtreating women, because this
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349 – Poster Frailty as a predictor of adverse outcomes in patients undergoing surgery for gynecologic malignancies E. Georgea, X. Zhangb, F. Simpkinsc, N.A. Latifc, R.L. GiuntoliIId, M.A. Morganc, K. Schmitzb, J.D. Wrighte, E.M. Koc. aHospital of University of Pennsylvania, Philadelphia, PA, USA, bPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, cUniversity of Pennsylvania, Philadelphia, PA, USA, dUniversity of Pennsylvania Health System, Philadelphia, PA, USA, eColumbia University College of Physicians and Surgeons, New York, NY, USA
Abstracts / Gynecologic Oncology 141 (2016) 2–208
147
University Medical Center and Weill Cornell Medical College, New York, NY, USA, bWeill Cornell Medical College, New York, NY, USA, cColumbia University, New York, NY, USA
doi:10.1016/j.ygyno.2016.04.382
Objectives: Single-site laparoscopy has proven to be a desirable option for patients undergoing gynecologic surgery, with some studies indicating improved cosmesis and less perioperative pain compared with standard approaches. This study describes the safety and feasibility of a novel robotic laparoendoscopic single-site surgery (R-LESS) platform as it is newly incorporated into a surgeon’s practice. Methods: A review was conducted of 82 women undergoing R-LESS at a single institution from September 2013 through August 2015. All surgeries were performed by a single gynecologic oncologist with extensive experience in robotic surgery. Operative times were collected prospectively for the first 51 cases. Clinical parameters including age, estimated blood loss, body mass index (BMI), prior abdominal surgeries, conversion to laparotomy, procedure type, uterine weight, length of hospital stay, and complications were retrospectively collected from medical charts. Results: A total of 81 surgeries were completed successfully with a single incision. Twelve surgeries were performed for cancer (1 ovary, 8 uterus, and 3 cervix). Seven patients underwent pelvic lymph node biopsy. The median total operative time for adnexal surgeries was 97 minutes (range, 57–177 minutes) and 128 minutes (range, 60– 275 minutes) for hysterectomies. Mean docking time halved from 7.8 minutes to 3.4 minutes in a comparison of the first 10 cases with the last 10 cases. Operative time and console time also steadily decreased with experience. Surgical times were longer with larger BMIs, but the console time decreased with experience regardless of BMI. The mean uterine weight was 161.3 g (range, 30–460 g). Complications included 2 umbilical hernias and 1 conversion to multiport. Conclusions: R-LESS is a feasible surgical platform for gynecologic procedures. As our surgical team gained experience, operative times decreased even as surgical complexity (BMI, number of prior abdominal surgeries) increased. Further study is needed to investigate the cost, benefits, and long-term outcomes of R-LESS.
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Objectives: The objective of this investigation was to use patientderived xenograft (PDX) models with and without PIK3CA gene mutation to understand the driving genomic events associated with the development of resistance to PI3K inhibition. Methods: With institutional approval, NOD/SCID mice bearing xenografts derived from 2 primary human endometrioid endometrial human tumors (ENCA1, ENCA2) underwent genotyping revealing ENCA1harbored PIK3CA and PTEN mutations, while ENCA2 demonstrated no detected mutations using the SNAPSHOT platform. Two arm cohorts (n = 12/arm) with equivalent tumor volumes received either NVP BKM-120 (30 mg/kg) or vehicle, and xenograft tumor volumes were assessed. Xenografts were harvested before therapy and at the point of sensitivity, resistance, or prolonged sensitivity. RNA was extracted for quantification using Illumina HiSEQ 2000 to determine the genome level changes in the ENCA1 and ENCA2 tumors. In the supervised analysis, using absolute-fold change (FC N 2) and P value (P b. 05), differentially expressed genes were identified at the points of resistance and prolonged sensitivity. Pattern, functional, and pathway analyses were used to explore the biological meaning of these gene signatures. Results: Both ENCA1 and ENCA2 manifested initial response to NVP BKM-120, and the 2 models had divergent sensitivity signatures. Pathway and functional analyses revealed key nodes in the 53 gene signatures associated with prolonged sensitivity were sustained abrogation of AKT and the mitogen-activated protein kinase (MAPK) signaling. While ENCA1 maintained prolonged sensitivity, ENCA2 developed resurgent growth. A 238 gene set was observed to have significant counterregulation with the development of resistance and was exclusive to ENCA2. Gene and pathway analysis demonstrated that resistance to PI3K inhibition was associated with marked increases in estrogen signaling and ubiquitination. Conclusions: These results highlight that genomic events conferring sensitivity are distinct, depending on the presence of PIK3CA mutation. While prolonged sensitivity to PI3K pathways inhibition appears to be dependent on sustained inhibition of AKT and MAPK signaling, resistance was associated with heightened estrogen and ubiquitin activity. These data provide rationale for pairing PI3K pathway inhibition with hormonal or ubiquitin blockade to improve durable antitumor response.
RO
351 – Poster Next-generation genomic signature highlights sustained AKT and estrogen receptor signaling as key mediators of resistance following phosphatidylinositol 3-kinase (PI3K) inhibition in patient-derived xenograft models with and without PIK3CA gene mutations W.B. Growdona, J.A. Rauh-Hainb, R. Fosterb, M. Bhasinc, B.R. Ruedab. a Harvard Medical School, Boston, MA, USA, bMassachusetts General Hospital, Boston, MA, USA, cBeth Israel Deaconess Medical Center, Boston, MA, USA
OF
may lead to poorer quality of life without apparent benefit. Introduction of palliative care measures at the time of recurrence and the use of hormonal or noncytoxic therapies should be considered.
doi:10.1016/j.ygyno.2016.04.383
352 – Poster Feasibility and learning curve of robotic laparoendoscopic single site surgery in gynecology A. Buckley de Meritensa, J.G. Kimb, N.L. Jonesa, H.E. Dinkelspielc, S. Chatterjeea, D. Guptab, T.A. Caputob, K.M. Holcombb. aNYPH, Columbia
doi:10.1016/j.ygyno.2016.04.384
353 – Poster Phase 1/2a study of double immune suppression blockade by combining a CSF1R inhibitor (pexidartinib/PLX3397) with an anti–PD-1 antibody (pembrolizumab) to treat advanced melanoma and other solid tumors J.C. Sachdeva, S. Hu-Lieskovanb, A. Patnaikc, P.D. Eisenbergd, A. Weisee, M.A. Hutchinsonf, B. Westg, C. Gauseh, S. Tongg, A. Ribasb. a Honor Health - VGPCC, Scottsdale, AZ, USA, bDavid Geffen School of Medicine at UCLA, Los Angeles, CA, USA, cSTART, San Antonio, TX, USA, d Marin Cancer Care, Greenbrae, CA, USA, eKarmanos Cancer Center/ Wayne State University, Detroit, MI, USA, fUniversity of California, San Francisco, San Francisco, CA, USA, gPlexxikon Inc., Berkeley, CA, USA, h Merck & Company, Inc., Whitehouse Station, NJ, USA Objectives: Tumor-associated macrophages (TAMs) support tumor growth and cause tumor resistance to chemotherapy and radiation therapy. Myeloid-derived suppressor cells (MDSCs) suppress antitumor immunity and cause resistance to PD-1 inhibition. TAMs and MDSCs are both regulated in part by colony-stimulating factor 1 (CSF1), which signals via its receptor (CSF1R). Pexidartinib is an oral, small-molecule inhibitor of CSF1R. The normal function of PD-1, expressed on the cell surface of activated T cells, is to suppress excessive immune responses, eg, autoimmune reactions. Tumors use
Similarly, high-grade disease was driven by HPV16/18 in AAW with normal cytology and abnormal cytology (≥ASCUS). Likewise, looking at age deciles (from 21–59 years), the absolute risk of CIN3+ is always higher with HPV16/18 versus the 12 other hrHPV types for AAW irrespective of age (nonsignificant for N50 years because of the small number of cases) Conclusions: The ATHENA trial, the largest cervical cancer screening study to date in the United States, indicates that most cases of highrisk cervical disease are caused by HPV16/18. This is in spite of reports indicating an HPV genotype distribution difference in AAW and non-Hispanic Caucasian women and its impact on disease prevention with currently available HPV vaccines. This is similar to what has been documented in non-Hispanic Caucasian women. Therefore, this calls into question the clinical relevance of creating race-specific HPV vaccines.
gynecologic cancer surgery, namely uterine and ovarian cancer, and may aid in preoperative counseling. Table 1 Preoperative Risk Factors Included in the mFI.
OF
146
doi:10.1016/j.ygyno.2016.04.380
doi:10.1016/j.ygyno.2016.04.381
350 – Poster The impact of percentage of time on chemotherapy on survival in recurrent ovarian cancer T. Febbraroa,b, A. Puglisib, Y. Zhoub, J.A. Hurteaub, C.V. Kirschnerb, G.C. Rodriguezb, K.T. Wardc, E.D. Mooreb. aThe University of Chicago Medicine, Chicago, IL, USA, bNorthshore University Health System, Evanston, IL, USA, cPresence Saint Francis Hospital, Evanston, IL, USA
Objectives: We sought to determine if the modified frailty index (mFI) correlates with morbidity and mortality in patients undergoing gynecologic cancer surgery. Predicting outcomes is important in preoperative counseling and surgical planning. The concept of frailty is emerging as a potential tool for predicting worse surgical outcomes. It is defined as an increase in one’s vulnerability for developing dependency or death because of a loss of physical or mental reserve, often in the absence of a defined comorbidity. Methods: Patients who underwent gynecologic cancer surgery from 2006 to 2012 in the National Surgical Quality Improvement Program (NSQIP) database were analyzed. mFI was calculated using 11 preoperative variables. (See Table 1.) Associations between mFI and readmission, major complications, and 30-day mortality were assessed. A multiviariable logistic regression model was used to predict adverse outcomes, after adjusting for age, race, and body mass index. Results: A total of 13,093 patients who had surgery for a gynecologic malignancy were identified (6,728 [51.4%] with uterine, 2,765 [21.1%] with ovarian, 2,373 [18.1%] with cervical, and 1,227 [9.4%] with other gynecologic cancers). For all gynecologic malignancies, there were 654 (5.0%) readmissions, 890 (6.8%) patients with 1 or more major complications, and 93 (0.008%) deaths within 30 days. When including all women who underwent gynecologic cancer surgery, increasing mFI was significantly associated with increased risk for major complications (OR 1.19, 95% CI 1.09–1.30, P b .001) and 30-day mortality (OR 1.49, 95% CI 1.18–1.87, P = .001), but not for readmission. For example, 30-day mortality increased from 0.4% in patients with an mFI of 0, to 7.6% in those with an mFI of 0.3 or higher. When analyzing each malignancy individually, this trend was noted in both uterine and ovarian cancer patients, both younger and older than 65 years of age. For example, 30-day mortality increased from 0.4% in uterine cancer patients with an mFI of 0, to 5.7% in those with an mFI of 0.3 or higher, and from 0.8% to 12.5% in ovarian cancer patients. There was no trend found for cervical or other gynecologic cancer patients. Conclusions: The mFI can be calculated with routinely collected clinical data and is predictive of adverse outcomes in patients undergoing
Objectives: Most women with ovarian cancer achieve remission after first-line chemotherapy. However, the majority will experience recurrence, and many women will receive additional palliative chemotherapy yet eventually succumb to their disease. With the benefit of additional palliative chemotherapy debatable, balancing quality of life with chemotherapy toxicity is of paramount importance. This study aims to determine whether additional time receivng salvage chemotherapy leads to improved overall survival (OS) in those with recurrent ovarian cancer. Methods: A single institutional cancer registry was queried to identify women treated for recurrent ovarian cancer from 2004 to 2014. A retrospective chart review was performed to abstract clinical data on a randomly selected sample of 100 women. Patients were divided into tertiles based on percentage of time receiving chemotherapy from recurrence to death with the first tertile having the smallest percentage of time on chemotherapy and the third tertile having the greatest percentage of time on chemotherapy. KaplanMeier and the log-rank tests were used to compare survival between groups. Results: Among all recurrent ovarian cancer patients, a greater percentage of time on chemotherapy from recurrence to death was associated with poorer OS (first tertile 44 months vs third tertile 31 months, P = .02). In those that became platinum resistant, a greater percentage of time of chemotherapy was associated with poorer OS whereas in platinum-sensitive women a greater percentage of time on chemotherapy did not improve OS (platinum resistant: first tertile 47 months vs third tertile 31 months, P = .003; platinum sensitive: first tertile 42 months vs third tertile 53 months, P = .31). In platinum-resistant women, a greater percentage of time on chemotherapy from platinum resistance to death also did not improve OS (first tertile 39 months vs third tertile 34 months, P = .23). Conclusions: In this cohort of recurrent ovarian cancer patients, a greater percentage of time on chemotherapy did not lead to improved survival, and in some cases, worsened survival. In a palliative setting, caution should be taken against overtreating women, because this
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CO
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349 – Poster Frailty as a predictor of adverse outcomes in patients undergoing surgery for gynecologic malignancies E. Georgea, X. Zhangb, F. Simpkinsc, N.A. Latifc, R.L. GiuntoliIId, M.A. Morganc, K. Schmitzb, J.D. Wrighte, E.M. Koc. aHospital of University of Pennsylvania, Philadelphia, PA, USA, bPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, cUniversity of Pennsylvania, Philadelphia, PA, USA, dUniversity of Pennsylvania Health System, Philadelphia, PA, USA, eColumbia University College of Physicians and Surgeons, New York, NY, USA
Abstracts / Gynecologic Oncology 141 (2016) 2–208
147
University Medical Center and Weill Cornell Medical College, New York, NY, USA, bWeill Cornell Medical College, New York, NY, USA, cColumbia University, New York, NY, USA
doi:10.1016/j.ygyno.2016.04.382
Objectives: Single-site laparoscopy has proven to be a desirable option for patients undergoing gynecologic surgery, with some studies indicating improved cosmesis and less perioperative pain compared with standard approaches. This study describes the safety and feasibility of a novel robotic laparoendoscopic single-site surgery (R-LESS) platform as it is newly incorporated into a surgeon’s practice. Methods: A review was conducted of 82 women undergoing R-LESS at a single institution from September 2013 through August 2015. All surgeries were performed by a single gynecologic oncologist with extensive experience in robotic surgery. Operative times were collected prospectively for the first 51 cases. Clinical parameters including age, estimated blood loss, body mass index (BMI), prior abdominal surgeries, conversion to laparotomy, procedure type, uterine weight, length of hospital stay, and complications were retrospectively collected from medical charts. Results: A total of 81 surgeries were completed successfully with a single incision. Twelve surgeries were performed for cancer (1 ovary, 8 uterus, and 3 cervix). Seven patients underwent pelvic lymph node biopsy. The median total operative time for adnexal surgeries was 97 minutes (range, 57–177 minutes) and 128 minutes (range, 60– 275 minutes) for hysterectomies. Mean docking time halved from 7.8 minutes to 3.4 minutes in a comparison of the first 10 cases with the last 10 cases. Operative time and console time also steadily decreased with experience. Surgical times were longer with larger BMIs, but the console time decreased with experience regardless of BMI. The mean uterine weight was 161.3 g (range, 30–460 g). Complications included 2 umbilical hernias and 1 conversion to multiport. Conclusions: R-LESS is a feasible surgical platform for gynecologic procedures. As our surgical team gained experience, operative times decreased even as surgical complexity (BMI, number of prior abdominal surgeries) increased. Further study is needed to investigate the cost, benefits, and long-term outcomes of R-LESS.
UN
CO
RR
EC
TE
DP
Objectives: The objective of this investigation was to use patientderived xenograft (PDX) models with and without PIK3CA gene mutation to understand the driving genomic events associated with the development of resistance to PI3K inhibition. Methods: With institutional approval, NOD/SCID mice bearing xenografts derived from 2 primary human endometrioid endometrial human tumors (ENCA1, ENCA2) underwent genotyping revealing ENCA1harbored PIK3CA and PTEN mutations, while ENCA2 demonstrated no detected mutations using the SNAPSHOT platform. Two arm cohorts (n = 12/arm) with equivalent tumor volumes received either NVP BKM-120 (30 mg/kg) or vehicle, and xenograft tumor volumes were assessed. Xenografts were harvested before therapy and at the point of sensitivity, resistance, or prolonged sensitivity. RNA was extracted for quantification using Illumina HiSEQ 2000 to determine the genome level changes in the ENCA1 and ENCA2 tumors. In the supervised analysis, using absolute-fold change (FC N 2) and P value (P b. 05), differentially expressed genes were identified at the points of resistance and prolonged sensitivity. Pattern, functional, and pathway analyses were used to explore the biological meaning of these gene signatures. Results: Both ENCA1 and ENCA2 manifested initial response to NVP BKM-120, and the 2 models had divergent sensitivity signatures. Pathway and functional analyses revealed key nodes in the 53 gene signatures associated with prolonged sensitivity were sustained abrogation of AKT and the mitogen-activated protein kinase (MAPK) signaling. While ENCA1 maintained prolonged sensitivity, ENCA2 developed resurgent growth. A 238 gene set was observed to have significant counterregulation with the development of resistance and was exclusive to ENCA2. Gene and pathway analysis demonstrated that resistance to PI3K inhibition was associated with marked increases in estrogen signaling and ubiquitination. Conclusions: These results highlight that genomic events conferring sensitivity are distinct, depending on the presence of PIK3CA mutation. While prolonged sensitivity to PI3K pathways inhibition appears to be dependent on sustained inhibition of AKT and MAPK signaling, resistance was associated with heightened estrogen and ubiquitin activity. These data provide rationale for pairing PI3K pathway inhibition with hormonal or ubiquitin blockade to improve durable antitumor response.
RO
351 – Poster Next-generation genomic signature highlights sustained AKT and estrogen receptor signaling as key mediators of resistance following phosphatidylinositol 3-kinase (PI3K) inhibition in patient-derived xenograft models with and without PIK3CA gene mutations W.B. Growdona, J.A. Rauh-Hainb, R. Fosterb, M. Bhasinc, B.R. Ruedab. a Harvard Medical School, Boston, MA, USA, bMassachusetts General Hospital, Boston, MA, USA, cBeth Israel Deaconess Medical Center, Boston, MA, USA
OF
may lead to poorer quality of life without apparent benefit. Introduction of palliative care measures at the time of recurrence and the use of hormonal or noncytoxic therapies should be considered.
doi:10.1016/j.ygyno.2016.04.383
352 – Poster Feasibility and learning curve of robotic laparoendoscopic single site surgery in gynecology A. Buckley de Meritensa, J.G. Kimb, N.L. Jonesa, H.E. Dinkelspielc, S. Chatterjeea, D. Guptab, T.A. Caputob, K.M. Holcombb. aNYPH, Columbia
doi:10.1016/j.ygyno.2016.04.384
353 – Poster Phase 1/2a study of double immune suppression blockade by combining a CSF1R inhibitor (pexidartinib/PLX3397) with an anti–PD-1 antibody (pembrolizumab) to treat advanced melanoma and other solid tumors J.C. Sachdeva, S. Hu-Lieskovanb, A. Patnaikc, P.D. Eisenbergd, A. Weisee, M.A. Hutchinsonf, B. Westg, C. Gauseh, S. Tongg, A. Ribasb. a Honor Health - VGPCC, Scottsdale, AZ, USA, bDavid Geffen School of Medicine at UCLA, Los Angeles, CA, USA, cSTART, San Antonio, TX, USA, d Marin Cancer Care, Greenbrae, CA, USA, eKarmanos Cancer Center/ Wayne State University, Detroit, MI, USA, fUniversity of California, San Francisco, San Francisco, CA, USA, gPlexxikon Inc., Berkeley, CA, USA, h Merck & Company, Inc., Whitehouse Station, NJ, USA Objectives: Tumor-associated macrophages (TAMs) support tumor growth and cause tumor resistance to chemotherapy and radiation therapy. Myeloid-derived suppressor cells (MDSCs) suppress antitumor immunity and cause resistance to PD-1 inhibition. TAMs and MDSCs are both regulated in part by colony-stimulating factor 1 (CSF1), which signals via its receptor (CSF1R). Pexidartinib is an oral, small-molecule inhibitor of CSF1R. The normal function of PD-1, expressed on the cell surface of activated T cells, is to suppress excessive immune responses, eg, autoimmune reactions. Tumors use