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Purpose Using real-world data, interstitial lung disease (ILD) prevalence before and after HER2-directed therapy was estimated. Potential ILD risk factors in patients receiving HER2-directed therapy for metastatic breast cancer (mBC) were evaluated. Methods Adults with HER2-directed therapy for mBC initiated between September 25, 1998, and February 22, 2020 were, included. ILD was defined broadly as one or more of 64 lung conditions. Patients were followed until incident ILD, death, last contact, or study end. Results In total, 533 patients were identified with median age at mBC of 57, 51% had de novo mBC, 43% were ever smokers, 30% had lung metastases, 9% had thoracic radiation, 6% had chronic obstructive pulmonary disease, and 16% had prevalent ILD. ILD cumulative incidence at one year was 9% (95% CI 6%, 12%), with a median follow-up of 23 months. Smoking (HR 2.2, 95% CI 1.1, 4.8) and Black/African-American race (HR 3.4, 95% CI 1.6, 7.5) were significantly associated with ILD; HRs for preexisting lung conditions (HR 1.8, 95% CI 0.9, 3.8) and thoracic radiation (HR 2.3, 95% CI 0.8, 7.1) were not statistically significant. Prevalent ILD was associated with 13-fold greater occurrence of incident ILD. 85% of patients with prevalent or incident ILD were symptomatic. Conclusions This real-world population of patients with mBC had a high prevalence of ILD prior to HER2-directed therapy, reflecting the multifactorial causation of interstitial lung changes. The cumulative incidence of ILD in patients receiving HER2-directed therapy for mBC augments prior reports. Symptomatic presentation suggests an opportunity for early intervention.

Background: Germline (g)BRCA1/2 mutations represent approximately 5% of metastatic breast cancer. Poly ADP-ribose polymerase inhibitors (PARPi) have shown improved clinical outcomes, a manageable toxicity profile, and favorable patient (pt)-reported outcomes versus chemotherapy in pts with gBRCA1/2 mutated HER2- locally advanced or metastatic breast cancer. With the advent of PARPi, clinical guidelines have broadened eligibility criteria for gBRCA1/2 testing. However, limited information is available on the impact of the COVID-19 pandemic on gBRCA1/2 testing rates. We assessed trends and factors associated with gBRCA1/2 testing in pts with HER2- ABC before and during the COVID-19 pandemic. Methods: This retrospective study included pts from the Syapse LHN, a longitudinal database of pts with cancer cared for in community-based, integrated care delivery networks in 25 states in the United States. Pts were eligible for gBRCA1/2 testing from initial ABC diagnosis until death or date of last contact with the participating health system. Information on gBRCA1/2 testing was obtained from scaled sources and further curated by Certified Tumor Registrars. Logistic regression evaluated the associations between age at diagnosis, family history of relevant cancer, race/ethnicity, median household income, health system, and diagnosis year with gBRCA1/2 testing among HER2- ABCs; models included hormone receptor status. Results: The study population included 1769 pts with HER2- ABC, including 577 pts with triple negative ABC initially diagnosed from 2010: 96% were women, 69% were non-Hispanic White, and 94% had an estimated median household income >$30,000 USD; median age at initial diagnosis was 61 years. The percentage of pts ever gBRCA1/2-tested among those eligible increased over time: 26%, 28%, and 31% by end of 2018, 2019, and 2020, respectively. Similarly, the percentages of new testing among eligible but not previously tested pts increased from 2018-March 2020, decreased from April-September 2020, and trended upwards thereafter (Table 1). In logistic regression models combining data from pre- and post-COVID-19 periods, family history of relevant cancer (odds ratio [OR]=1.9; 95% CI, 1.5-2.4), younger age at diagnosis (>65 reference; Table 1.Percentages of Newly gBRCA1/2-Tested Pts with HER2- ABC Who Were Eligible for Testing Anytime During the Time Period and Not Previously TestedTime Period2018, % (n/N)2019, % (n/N)2020, % (n/NJanuary-March2.3 (10/427)2.7 (14/512)4.3 (23/537)April-June2.9 (13/447)3.4 (18/536)2.8 (14/495)July-September4.3 (20/468)4.7 (27/569)2.5 (13/517)October-December1.9 (9/478)3.1 (17/548)3.5 (16/456)Total8.4 (52/622)10.0 (76/757)8.8 (66/747)A pt diagnosed in February and tested in April of 2018 would be included in the denominator (N) for January-March and April-June of 2018 and in the numerator (n) for April-June of 2018. Citation Format: Alexander Niyazov, Monika Izano, Colden Johanson, Sheetal Walters, Anna Berry, Bhakti Arondekar, A. Douglas Laird, Lillian Shahied Arruda, Henry Kaplan. Germline BRCA1/2 mutation testing in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC): A real-world study in the Syapse Learning Health Network (LHN) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-05.

Background. Clinical trials (CT) include patients (pts) satisfying eligibility criteria including normal organ function and low comorbidity. Real-world outcomes for pts with aNSCLC receiving ICIs in 2L were compared based on whether pts met CT eligibility criteria. Methods. 2L- associated outcomes were compared between pts with aNSCLC diagnosed between 04/01/2015 - 12/31/2020 in US community health systems that fulfilled or failed to fulfill CT eligibility criteria. CT-eligible (CTE) pts had at 2L: performance status of 0-1; normal renal, hepatic, and bone marrow function; no evidence of Hepatitis B or C, HIV, rheumatic diseases, or interstitial lung disease. Pts were CT-ineligible (CTI) if they failed to meet one or more of these criteria. Follow-up spanned 2L start to the first of: outcome of interest, death, or study end on 06/30/2021. Outcomes were evaluated in pts receiving ICI monotherapy (monotherapy) or ICI + chemotherapy (combination). Results. Of the 505 pts in this analysis, 81% and 19% received monotherapy and combination, respectively; 19% of pts were CTE (76% monotherapy, 24% combination, Table). Overall, in ICI subgroups among monotherapy pts, pembrolizumab-treated pts had longer OS and TTNT; time to treatment discontinuation (TTD) was less variable across subgroups. CTE pts in the monotherapy group had longer OS, shorter TTNT, and similar TTD compared to CTI. Among combination pts, CTE had similar OS and TTD, but shorter TTNT compared to CTI. Conclusions. CTE pts appear to have longer survival than CTI pts with aNSCLC receiving ICI monotherapy, but not among pts receiving combination. TTNT was longer for CTI pts in both groups. In addition to CTE pts, some CTI pts appear to benefit from 2L ICI therapy. Time-to-event outcomes (months), median (95% CI) in the study cohort Monotherapy (N = 412) Monotherapy (N = 412) Monotherapy (N = 412) Monotherapy (N = 412) Combination (N = 93) Combination (N = 93) Combination (N = 93) Combination (N = 93) N (%) OS TTNT TTD N (%) OS TTNT TTD Atezolizumab 37 (9%) 7 (3-16) 9 (7-NA) 2 (1-3) 9 (10%) 6 (5-NA) NA (5-NA) 2 (1-NA) Nivolumab 234 (57%) 14 (9-18) 20 (15-NA) 2 (2-3) 9 (10%) 36 (6-NA) 23 (6-NA) 5 (3-NA) Pembrolizumab 138 (34%) 20 (16-28) NA (31-NA) 2 (1-3) 75 (80%) 12 (8-NA) 20 (15-NA) 1 (1-3) Overall - 15 (13-18) 23 (18-NA) 2 (2-2) - 11 (7-NA) 20 (10-NA) 2 (1-3) Trial-Eligible (all regimens) 72 (18%) 20 (12-NA) 19 (10-NA) 2 (2-3) 23 (25%) 11 (5-NA) 10 (7-NA) 3 (1-6) Trial-Ineligible(all regimens) 292 (70%) 13 (8-16) 26 (18-NA) 2 (2-2) 64 (69%) 11 (7-NA) 20 (9-NA) 2 (1-3) Unknown Trial Eligibility 47 (12%) - - - 6 (6%) - - - Citation Format: Hina Mohammed, Miso Kim, Mahder Teka, Monika Izano, Frank Wolf, Thomas Brown. A real world analysis: Impact of clinical trial eligibility criteria on clinical outcomes among patients with advanced non-small cell lung cancer (aNSCLC) receiving second line (2L) immune checkpoint inhibitor (ICI) therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6655.

Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults.