SAFFRON-103: a phase Ib study of sitravatinib plus tislelizumab in anti-PD-(L)1 refractory/resistant advanced melanoma.

Aim: Investigate TKI sitravatinib plus anti-PD-1 antibody tislelizumab in patients with unresectable/advanced/metastatic melanoma with disease progression on/after prior first-line anti-PD-(L)1 monotherapy. Methods: Open-label, multicenter, multicohort study (NCT03666143). Patients in the melanoma cohort (N = 25) received sitravatinib once daily plus tislelizumab every 3 weeks. The primary end point was safety and tolerability. Results: Treatment-emergent adverse events (TEAEs) occurred in all patients, with ≥grade 3 TEAEs in 52.0%. Most TEAEs were mild-or-moderate in severity, none were fatal, and few patients discontinued treatment owing to TEAEs (12.0%). Objective response rate was 36.0% (95% CI: 18.0-57.5). Median progression-free survival was 6.7 months (95% CI: 4.1-not estimable). Conclusion: Sitravatinib plus tislelizumab had manageable safety/tolerability in patients with anti-PD-(L)1 refractory/resistant unresectable/advanced/metastatic melanoma, with promising antitumor activity. Clinical Trial Registration: NCT03666143 (ClinicalTrials.gov).

Cancer survivorship programs for patients from culturally and linguistically diverse (CALD) backgrounds: a scoping review.

PURPOSE: People of Culturally and Linguistically Diverse (CALD) backgrounds face disparities in cancer care. This scoping review aims to identify the breadth of international literature focused on cancer survivorship programs/interventions specific to CALD populations, and barriers and facilitators to program participation. METHODS: Scoping review included studies focused on interventions for CALD cancer survivors after curative-intent treatment. Electronic databases: Medline, Embase, CINAHL, PsycInfo and Scopus were searched, for original research articles from database inception to April 2022. RESULTS: 710 references were screened with 26 included: 14 randomized (54%), 6 mixed-method (23%), 4 non-randomized experimental (15%), 2 qualitative studies (8%). Most were United States-based (85%), in breast cancer survivors (88%; Table 1), of Hispanic/Latinx (54%) and Chinese (27%) backgrounds. Patient-reported outcome measures were frequently incorporated as primary endpoints (65%), or secondary endpoints (15%). 81% used multi-modal interventions with most encompassing domains of managing psychosocial (85%) or physical (77%) effects from cancer, and most were developed through community-based participatory methods (46%) or informed by earlier work by the same research groups (35%). Interventions were usually delivered by bilingual staff (88%). 17 studies (77%) met their primary endpoints, such as meeting feasibility targets or improvements in quality of life or psychological outcomes. Barriers and facilitators included cultural sensitivity, health literacy, socioeconomic status, acculturation, and access. CONCLUSIONS: Positive outcomes were associated with cancer survivorship programs/interventions for CALD populations. As we identified only 26 studies over the last 14 years in this field, gaps surrounding provision of cancer survivorship care in CALD populations remain. IMPLICATIONS FOR CANCER SURVIVORS: Ensuring culturally sensitive and specific delivery of cancer survivorship programs and interventions is paramount in providing optimal care for survivors from CALD backgrounds.

Immune checkpoint inhibitors in ovarian cancer: where do we go from here?

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and despite advancements in therapeutics, most women unfortunately still succumb to their disease. Immunotherapies, in particular immune checkpoint inhibitors (ICI), have been therapeutically transformative in many tumour types, including gynaecological malignancies such as cervical and endometrial cancer. Unfortunately, these therapeutic successes have not been mirrored in ovarian cancer clinical studies. This review provides an overview of the ovarian tumour microenvironment (TME), particularly factors associated with survival, and explores current research into immunotherapeutic strategies in EOC, with an exploratory focus on novel therapeutics in navigating drug resistance.

Growing Teratoma Syndrome in the Setting of Sarcoidosis: A Case Report and Literature Review.

Growing teratoma syndrome (GTS) is rare and can mimic disease recurrence in patients with a history of immature teratoma. Benign hypermetabolic lymphadenopathy found on staging and surveillance computed tomography (CT) and positron emission tomography (PET) may lead to the presumption of metastatic malignancy. We report a case of a 38 year old with mixed mature and immature teratomas who developed new peritoneal masses after adjuvant chemotherapy despite a normalization of tumor markers. In addition to low FDG uptake observed in these peritoneal masses, a PET scan showed hypermetabolic lymphadenopathy and pulmonary and spleen lesions suggesting widespread metastases. Subsequent surgical resection confirmed a mixed pathology with GTS and sarcoidosis. We reviewed the current literature evidence of GTS and sarcoidosis as a benign cause of lymphadenopathy in cancer patients. We emphasize the importance of a tissue diagnosis before instituting therapy for presumed cancer recurrence to avoid potentially fatal diagnostic traps and management errors. A multiple disciplinary team approach is imperative in managing patients with suspected recurrent immature teratomas.

Tumor Response End Points as Surrogates for Overall Survival in Immune Checkpoint Inhibitor Trials: A Systematic Review and Meta-Analysis.

PURPOSE: Many immune checkpoint inhibitors (ICIs) have been approved on the basis of tumor response end points in nonrandomized trials, including objective response rate (ORR) and duration and depth of response. We aimed to assess the validity of these end points as surrogate end points for overall survival (OS) in patients with advanced solid tumors treated with ICIs at trial and treatment arm levels. METHODS: ICI trials in advanced solid cancers published between January 1, 2000, and March 31, 2020, were included. Correlations between ORR, durable response (DR) of ≥ 6 months, complete response (CR), and OS were assessed for treatment comparisons (trial-level) and for patients receiving ICI (arm-level), using weighted linear regression. RESULTS: Sixty-three trials were eligible, including 58 randomized controlled trials and 20 nonrandomized controlled trials (78 ICI arms and 30,815 patients). The majority were phase III (63%), and OS was the most common primary end point (40%). In relative treatment comparisons, correlations between ORR risk ratio and OS hazard ratio (HR), 6-month DR ratio and OS HR, and CR ratio and OS HR were r = 0.58, r = 0.62, and r = 0.42, respectively. Exploratory studies in melanoma, non-small-cell lung cancer, and other tumors showed similar results, although 6-month DR ratio was strongly correlated with OS HR (r = 0.89). Within ICI arms only, correlations between ORR and 12-month OS, 6-month DR and 12-month OS, and CR and 12-month OS were r = 0.76, r = 0.84, and r = 0.50, respectively, in all eligible trials. CONCLUSION: Relative measures of tumor response (ORR, 6-month DR, and CR) are poor surrogate end points for OS in ICI studies. However, ORR and 6-month DR are prognostic of 12-month OS in ICI studies supporting their use for screening activity of novel agents in early-phase nonrandomized trials.

Validation of Progression-Free Survival Rate at 6 Months and Objective Response for Estimating Overall Survival in Immune Checkpoint Inhibitor Trials: A Systematic Review and Meta-analysis.

Importance: Progression-free survival (PFS) rate at 6 months has been proposed as a potential surrogate for overall survival (OS) rate at 12 months for immune checkpoint inhibitor (ICI) trials but requires further assessment for validation. Objective: To validate 6-month PFS and objective response rate (ORR) as estimators of 12-month OS in the ICI arms of randomized clinical trials (RCTs). Data Sources: Electronic databases (Medline, EMBASE, and the Cochrane Central Register of Controlled Trials) were searched for ICI RCTs published between January 2000 and June 2019. Study Selection: Eligible studies were phase 2 and phase 3 ICI RCTs in advanced solid cancers that reported ORR, PFS, and OS. A total of 99 articles (from 60 studies) of 2502 articles were selected by consensus. Data Extraction and Synthesis: Data were screened and extracted independently. Estimation models for 12-month OS and to assess correlation coefficient between end points were developed using linear regression. Data were extracted in July 2019, and analyses were conducted in September 2019. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Validation of previously reported 6-month PFS and ORR estimation models for 12-month OS using contemporary RCTs. Calibration of 6-month PFS and ORR model-estimated vs observed 12-month OS in ICI arms were assessed by correlation coefficient (r) and weighted Brier scores. Secondary analyses were performed for subgroups (ie, ICI-only, ICI-combination, line of therapy, programmed cell death 1 ligand 1 selected, and unselected). Results: Data from 60 RCTs with 74 experimental ICI arms were used. The development data set included 25 arms from studies published January 2000 to January 2017. The estimation model for 12-month OS using 6-month PFS was: (1.06 × PFS6) + 0.16 + (0.04 × melanoma) - (0.03 × NSCLC) + (0 × other tumors), in which PFS6 indicates 6-month PFS and NSCLC indicates non-small cell lung cancer. The estimation model for 12-month OS using ORR was (0.15 × ORR) + 0.52 + (0 × melanoma) - (0.02 × NSCLC) - (0.01 × other tumors). A total of 49 arms from studies published after January 2017 to June 2019 formed the validation data set. When the models were applied on the validation data set, calibration between the 6-month PFS model estimated vs observed 12-month OS was good (r = 0.89; Brier score, 0.008), but poor for the ORR model (r = 0.47; Brier score, 0.03). Findings were similar across all subgroups. Conclusions and Relevance: The findings of this study suggest that the estimation model using 6-month PFS could reliably estimate 12-month OS in ICI trials. This study could assist in better selection and prioritization of ICI agents for testing in RCTs based on phase 2 single-arm RCT results.