everolimus / Generic mfg. - LARVOL DELTA

Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial. (PubMed, Lancet) - P=N/A | "In selected patients with permanently unresectable colorectal liver metastases, liver transplantation plus chemotherapy with organ allocation priority significantly improved survival versus chemotherapy alone. These results support the validation of liver transplantation as a new standard option for patients with permanently unresectable liver-only metastases."

Clinical • Journal • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • Transplantation • BRAF

Efficacy, safety and subgroup analysis of 177Lu-edotreotide vs everolimus in patients with grade 1 or grade 2 GEP-NETs: Phase III COMPETE trial (ESMO 2025) - P3 | "Table: 1706O Subgroup 177 Lu-edotreotide EVE p value Stratified HR (95%CI) n mPFS (months) n mPFS (months) Primary tumor origin GE-NET P-NET 88 119 23.9 24.5 43 59 12.0 14.7 0.1072 0.1033 0.7 (0.4-1.1) 0.7 (0.4-1.1) Tumour grade (local) Grade 1 Grade 2 43 164 30.0 21.8 29 73 23.7 9.2 0.8745 0.0031 0.9 (0.4-2.0) 0.6 (0.4-0.8) Prior medical therapy Treatment naïve (1 st line) Prior therapy (2 nd line) 30 177 Not reached 23.9 17 85 18.1 14.1 0.2666 0.0444 0.6 (0.2-1.5) 0.7 (0.5-1.0) Conclusions 177 Lu-edotreotide compared to EVE significantly improved PFS and ORR in patients with GEP-NETs. 177 Lu-edotreotide demonstrated meaningful clinical benefit across the subgroups (origin, grade and prior treatment) and was well-tolerated."

Clinical • P3 data • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • SSTR

Gedatolisib, a multi-target PI3K/AKT/mTOR (PAM) inhibitor, plus fulvestrant with or without palbociclib for second-line (2L) treatment of patients with HR+/HER2-/PIK3CA-wild type (WT) advanced breast cancer (ABC): updated results from the randomized, phase 3 VIKTORIA-1 trial (SABCS 2025) - "In preclinical studies, gedatolisib demonstrated superior potency and cytotoxicity compared to alpelisib, capivasertib, and everolimus, regardless of PI3K-pathway mutation status, and combinations of gedatolisib + fulvestrant, with and without palbociclib, were active in treatment-naive and resistant cell lines. These updated results support gedatolisib combination therapy as a potential new standard of care for the 2L treatment of patients with HR+/HER2-/PIK3CA WT ABC."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

A phase III study of combination therapy with everolimus plus lanreotide versus everolimus monotherapy for unresectable or recurrent gastroenteropancreatic neuroendocrine tumor (JCOG1901, STARTER-NET). (ASCO-GI 2025) - P3 | "The EVE/LAN provides statistically significant prolongation of PFS compared with EVE monotherapy, and the safety profile of EVE/LAN was manageable. The EVE/LAN might be a new standard treatment in the first-line setting for well-differentiated grade 1/2 GEP-NETs with poor prognostic factors."

Combination therapy • Monotherapy • P3 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trial. (PubMed, EBioMedicine) - P3 | "Tamoxifen intake in the evening/nighttime could be recommended in patients with high-risk HR+/HER2- BC while awaiting for results from further ET timing studies."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Efficacy and safety of [177Lu]Lu-edotreotide vs. everolimus in patients with grade 1 or grade 2 gastroenteropancreatic neuroendocrine tumours: COMPETE phase 3 trial (ENETS 2025) - "CONCLUSION The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful PFS benefit with [177Lu]Lu-edotreotide vs. everolimus. [177Lu]Luedotreotide was well tolerated, supporting its potential as a treatment option for GEP-NET."

Clinical • Late-breaking abstract • P3 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

A Randomized clinical trial evaluating the impact on survival and quality of life of 177Lutetium[Lu]-edotreotide versus everolimus in patients with neuroendocrine tumors of the lung and thymus: the LEVEL study (GETNE T-2217). (PubMed, BMC Cancer) - P3 | "The LEVEL trial will investigate if 177Lu-edotreotide has the potential to be incorporated as a standard treatment option for patients with NETs from the lung and Thymus."

Clinical • Clinical protocol • HEOR • Journal • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR • SSTR2

Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial. (PubMed, Nat Med) - P2 | "We subsequently tested the effects of transient versus chronic inhibition of autophagy with chloroquine or hydroxychloroquine (HCQ) and mTOR signaling with rapamycin (RAPA) or everolimus (EVE) on residual tumor cell (RTC) burden and recurrence-free survival (RFS). These findings provide proof-of-concept that targeting dormant RTCs with HCQ, EVE or their combination in breast cancer survivors or mouse models depletes minimal residual disease, warranting a definitive human randomized controlled trial. ClinicalTrials.gov registration: NCT03032406 ."

Journal • P2 data • Breast Cancer • Oncology • Solid Tumor

LEVER: PHASE II TRIAL OF LEVONORGESTREL INTRAUTERINE DEVICE ALONE OR IN COMBINATION WITH THE MTORC1 INHIBITOR EVEROLIMUS FOR THE TREATMENT OF ATYPICAL ENDOMETRIAL HYPERPLASIA AND EARLY-STAGE ENDOMETRIAL CANCER (IGCS 2025) - "Stage 1: 94 patients (61 AEH, 33 G1EEC, median age 36) were treated. Of 91 evaluable patients, 3-month response rate was 59.3% (90% CI: 48.2-69.6; 54 complete response (CR), 35 stable disease (SD), and 2 progressive disease (PD)). Stage 2: 42 patients (22 AEH, 20 G1EEC) were treated."

Combination therapy • P2 data • Endometrial Cancer • Oncology • Solid Tumor

A multicenter randomized phase II trial of lenvatinib plus everolimus versus cabozantinib in patients with metastatic clear cell RCC that progressed on PD-1 immune checkpoint inhibition (LenCabo). (PubMed, Ann Oncol) - "In this randomized phase II trial in metastatic ccRCC that progressed on prior PD-1 ICIs, lenvatinib + everolimus significantly prolonged PFS over cabozantinib. As the first head-to-head comparison of contemporary second-line or later treatments after ICI, these results are relevant to treatment sequencing and inform oncology practice."

Checkpoint inhibition • Journal • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Streptozotocin plus 5-fluorouracil followed by everolimus or the reverse sequence in patients with advanced pancreatic neuroendocrine tumors (SEQTOR-GETNE phase III study): a randomized clinical trial. (PubMed, ESMO Open) - "STZ/5-FU and everolimus were not statistically different in PFS rates, but STZ/5-FU achieved higher response rates."

Clinical • Journal • P3 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

EFFECTIVENESS OF STATIN THERAPY FOR ELEVATED LIPID LEVELS IN PATIENTS ON MTOR INHIBITORS AFTER HEART TRANSPLANTATION (WRMC 2026) - "Randomized control trials have demonstrated that one therapeutic strategy to slow the progression of CAV is the use of mTOR inhibitors (mTORi), including sirolimus and everolimus...Methods Used: Between 2010 to 2024, we assessed 41 HTx recipients who were transitioned from pravastatin, a low potency statin, to a high potency statin, specifically rosuvastatin or atorvastatin, after initiating mTORi therapy... Switching patients to high potency statin therapy effectively lowered lipid levels in heart transplant recipients on mTORis. Statin intensification (select dosing) appears safe and well tolerated in this population."

Clinical • Cardiovascular • Dyslipidemia • Metabolic Disorders • Transplantation

Fruquintinib monotherapy as second-line (2L) treatment in locally advanced or metastatic renal cell carcinoma (RCC): Results from phase II part of FRUSICA-2 (ESMO Asia 2025) - P2/3 | "Background: FRUSICA-2 is a randomized, open-label, active-controlled phase 2/3 study (NCT05522231) designed to evaluate the efficacy and safety of Fruquintinib (F) + Sintilimab versus Axitinib or Everolimus monotherapy for 2L treatment of RCC. Results from this F monotherapy of the FRUSICA-2 indicated a comparable anti-tumor efficacy compared with other 2L VEGFR-TKI monotherapies, along with a manageable safety profile in 2L RCC pts after first-line VEGFR-TKI therapy."

Clinical • Metastases • Monotherapy • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Giredestrant (GIRE), an oral selective estrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients with ER-positive, HER2-negative, advanced breast cancer (ER+, HER2– aBC) after prior treatment with a CDK4/6 inhibitor (i): Primary results of the Phase III evERA BC trial (DKK 2026) - No abstract available

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway."

Journal • P2 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • Neutropenia • Oncology • Solid Tumor • Triple Negative Breast Cancer • AR • HER-2

NF1/2 mutations predict favorable benefit from immune checkpoint inhibitor-based therapies over VEGFR/mTOR inhibitors in clear cell renal cell carcinoma. (PubMed, Clin Exp Med) - "This tendency was not changed by everolimus (HR = 2.66), but was abrogated slightly by sunitinib (HR = 1.59) and considerably by ICI-based therapies, including nivolumab monotherapy (HR = 1.12), atezolizumab plus bevacizumab (HR = 1.10), and avelumab plus axitinib (HR = 0.69). Overall, our findings suggest that NF1/2 mutations can serve as predictive biomarkers for favorable benefits from ICI-based treatments over VEGFR/mTOR inhibitors in advanced ccRCCs."

Checkpoint inhibition • IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Inflammatory Arthritis • Oncology • Solid Tumor • NF1

Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs) in the CheckMate 025 trial. (ASCO 2024) - P3 | "We aimed to characterize the association between a germline IL7 SNP (rs16906115) and AEs in a prospective clinical trial of patients with mRCC treated with nivolumab (NIVO) or everolimus (EVE). The IL7 SNP (rs16906115) is associated with significantly higher rates of grade 2+ AEs, including recurrent events, in pts with mRCC treated with NIVO but not with EVE, with no effect on survival outcomes. These results affirm the SNP's predictive potential as a biomarker for irAEs to guide therapeutic decisions in pts treated with ICIs."

Adverse events • IO biomarker • Gastrointestinal Disorder • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • IL7

STELLAR-304: A randomized phase III study of zanzalintinib (XL092) and nivolumab in non-clear cell renal cell carcinoma (nccRCC) (ESMO 2023) - P3 | "Sunitinib is the only TKI to have shown a clinical benefit (vs everolimus) in a broad range of histologic subtypes of metastatic nccRCC (Armstrong et al. The secondary endpoint is OS; safety will also be assessed. STELLAR-304 is currently recruiting patients in 29 countries in Europe, North and South America, and the Asia-Pacific region."

Clinical • P3 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Medullary Carcinoma • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • AXL • KDR

Association of IL7 germline variants with immune-related adverse events (irAEs) in cancer patients (pts) treated with immune checkpoint inhibitors (ICIs). (ASCO 2025) - P3 | " In this pooled analysis, we included 1,205 pts from the CheckMate-025 trial (CM025, NCT01668784) with renal cell carcinoma (RCC) who received either nivolumab (NIVO) or everolimus (EVE), from the BinTA-0037 (BTA-037, NCT03631706) in non-small cell lung cancer (NSCLC) treated with pembrolizumab (PEMBRO), and from the Asan ICI-treated pan-cancer cohort. The IL7 SNP (rs7816685) is associated with a higher risk of immune toxicity in pts treated with ICI. Overall, our findings support the use of this germline biomarker for irAE risk stratification, and pave the way for future functional studies. Adjusted hazard ratios (HRs) from multivariable Cox models adjusting for baseline covariates in each cohort."

Adverse events • Checkpoint inhibition • Clinical • IO biomarker • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • IL7

Validation of a 15-Gene Prognostic Signature in Metastatic Clear Cell Renal Cell Carcinoma. (PubMed, JCO Precis Oncol) - "The 15G score was independently prognostic in metastatic ccRCC among patients receiving different systemic therapy regimens."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

A phase II trial of sitravatinib plus nivolumab after progression on prior immune checkpoint inhibitor (ICI) in patients with metastatic clear cell renal cell carcinoma (ccRCC). (ASCO 2024) - P2 | " In this investigator-initiated, phase II, multicenter trial (NCT04904302), patients with progressive metastatic ccRCC after 1-2 lines of treatment were enrolled into three cohorts: Cohort A) progression on 1L nivolumab + ipilimumab, Cohort B) progression on 1L pembrolizumab + axitinib or 2L anti-PD-1 therapy after receiving 1L VEGF-targeted monotherapy, Cohort C) progression on 1L or 2L cabozantinib or lenvatinib +/- everolimus either before, after, or in combination with anti-PD-1 ICI... In this small phase 2 trial with limited sample size due to early termination, sitravatinib plus nivolumab demonstrated a manageable safety profile and produced modest clinical benefit. The observed responses occurred in patients who did not receive prior treatment with cabozantinib or lenvatinib."

Checkpoint inhibition • Clinical • Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Sarcoma • Solid Tumor

Analysis of long-term efficacy outcomes from the CheckMate 025 (CM 025) trial comparing nivolumab (NIVO) vs everolimus (EVE) based on ≥ 7 years (yrs) of follow-up in pre-treated patients (pts) with advanced renal cell carcinoma (aRCC) (ESMO 2022) - P3 | "Conclusions NIVO continues to demonstrate significant survival benefit vs EVE at ≥ 7 yrs follow-up, which is expected to be sustained over a pts lifetime. Analyses of pts with OS ≥ 7 yrs in the trial further highlight the likelihood of better treatment response and greater lifetime survival benefits observed with NIVO vs EVE."

Clinical • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Association of a Germline Single Nucleotide Polymorphism (SNP) in the Interleukin-7 (IL7) Gene with Immune-Related Adverse Events (irAEs) (KCRS 2024) - P3 | "Methods In the CheckMate-025 (CM025) trial (NCT01668784), involving patients with metastatic renal cell carcinoma (mRCC) randomized to either nivolumab (NIVO) or everolimus (EVE), whole-exome sequencing (WES) data from tumor and peripheral blood samples were analyzed...Results In total, 534 pts were included (NIVO: n=189, PEMBRO: n=152, EVE: n=193), among which 82 (15.4%) were SNP+...Conclusions The IL7 SNP (rs16906115) is associated with significantly higher rates of grade 2+ AEs, including recurrent events, in pts with mRCC or mNSCLC treated with single agent PD-1 inhibitors but not with non-ICI regimens, with no effect on survival and efficacy outcomes. These results confirm the SNP’s predictive potential as a biomarker for irAEs to guide therapeutic decisions in pts treated with ICIs."

Adverse events • IO biomarker • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • IL7

Clinical and biomarker subgroup analysis of evERA Breast Cancer: A Phase III trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor (SABCS 2025) - P3 | "Methods Pts who had ER+, HER2- aBC with disease progression (PD) post-CDK4/6i + ET in the aBC setting, or relapse during/after CDK4/6i + ET in the adjuvant setting, were randomized 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane, fulvestrant, or tamoxifen) + E until PD or unacceptable toxicity. Conclusions GIRE + E led to clinically meaningful improvements in INV-PFS vs SOC ET + E irrespective of PIK3CAm and PIK3CA/AKT1/PTEN alt, and other key relevant subgroups, regardless of ESR1m status. These data support the use of GIRE + E vs SOC ET + E in pts with ER+, HER2- aBC post-CDK4/6i + ET."

Biomarker • Clinical • Metastases • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA • PTEN

Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study (SABCS 2025) - " ELEVATE is evaluating elacestrant combined with everolimus, alpelisib, capivasertib, abemaciclib, ribociclib,or palbociclib to address different resistance mechanisms...PFS benefit was consistent across subgroups, including those with visceral metastases, prior fulvestrant or primary ET resistance... Elacestrant in combination shows a consistent PFS benefit irrespective of ESR1m status in pts with ER+/HER2-mBC after progressive disease on ET ± prior CDK4/6i. Elacestrant has the potential to become an ET backbone for combination strategies with targeted agents, supporting an all-oral approach that may delay the need for chemo or ADC-based regimens in this patient population. Table 1:Phase 2 mPFS, mo[95% CI] in all patients and subgroupsNR, not reached"

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA