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November 2022

In POSEIDON study, a treatment-naive patients with metastatic non-small cell lung cancer (NSCLC), tremelimumab (anti-CTLA-4 antibody) plus durvalumab (anti-PD-L1 antibody) and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in median Overall Survival (OS) [14 months vs 11.7 months] and median Progression Free Survival (PFS) [6.2 months vs 4.8 months] compared to platinum-based chemotherapy. The addition of tremelimumab to durvalumab and chemotherapy led to more durable responses hence FDA approved this combination for metastatic NSCLC in a front-line setting. (Ref: Johnson ML et al. Clin Oncol. Nov 3, 2022 and  U.S.FDA. Gov. Nov 10, 2022)

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In this Phase III study (CHOICE-01), patients with treatment-naive, advanced NSCLC with EGFR/ALK mutations, treatment with toripalimab (a humanized IgG4K monoclonal antibody specific for human PD-1) in combination with chemotherapy showed significantly better PFS (median PFS 13.1 v 5.5 months). This study supports the use of toripalimab in combination with chemotherapy as a front-line treatment option for patients with advanced NSCLC without EGFR/ALK driver mutations. (Ref: Wang Z et al. J Clin Oncol. Oct 7, 2022)

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In patients with advanced NSCLC without EGFR, ALK, or ROS1 genomic tumor aberrations, treatment with cemiplimab plus chemotherapy showed a consistent relationship between ORR and baseline PD-L1 expression, with benefits versus chemotherapy alone seen across all levels of baseline PD-L1 expression; there was also a clear association between a continuous measure of changes in tumor size over time and baseline PD-L1 expression. Cemiplimab is only the second anti-PD-1/PD-L1 agent to show efficacy in advanced NSCLC as both monotherapy and in combination with chemotherapy for both squamous and non-squamous histologies. (Ref: Gogishvili M et al. Nat Med. Aug 25, 2022)
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In patients with pretreated germline BRCA1/2 breast cancer who had received a median of two prior chemotherapy lines for advanced disease, treatment with Lurbinectedin (a selective inhibitor of oncogenic transcription) showed an ORR of 28.6% (95% CI 11.3% to 52.2%), median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. This study showed the activity of lurbinectedin in germline BRCA1/2 breast cancer with a predictable and manageable safety profile. (Ref: Boni V et al, ESMO Open. Aug 26, 2022)
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Indoleamine 2,3- dioxygenase 1 (IDO1) is a cytosolic heme-containing enzyme that functions to catalyze tryptophan (Trp) degradation and kynurenine (Kyn) production, and the Trp:Kyn ratio reflects IDO1 activity. Tobacco carcinogens upregulate IDO1. Clinically, smoker patients with non-small-cell lung cancer (NSCLC) exhibited high IDO1 levels and low Trp/ Kyn ratios. In NSCLC patients, smokers with lower IDO1 responded better to anti-PD1 antibody treatment than those with higher IDO1. The data indicate that tobacco smoke induces IDO1 to catabolize Trp metabolism and immune suppression to promote carcinogenesis, and lower IDO1 might be a potential biomarker for anti-PD1 antibodies in smoker patients, whereas IDO1-high smoker patients might benefit from IDO1 inhibitors in combination with anti-PD1 antibodies. ( Ref: Liang F et al. Signal Transduct Target Ther. Sep 7, 2022)
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In patients with advanced GIST who progressed on or were intolerant to first-line treatment with imatinib, ripretinib, a switch-control TKI, showed comparable median PFS as sunitinib, suggesting that ripretinib is active as second-line therapy for GIST. Additionally, ORR for patients receiving ripretinib in the KIT exon 11 population was higher compared with patients receiving sunitinib. Ripretinib demonstrated a more favorable safety profile and better responses on PRO measures than sunitinib. (Ref: Bauer S et al. J Clin Oncol. Aug 10, 2022)
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In 50 patients with advanced EGFR exon 20-mutant NSCLC, treatment with poziotinib showed confirmed ORRs of 31% by blinded independent review, with a median PFS of 5.5 months. Preclinical studies, in silico modeling, and molecular dynamics simulations showed that the poziotinib sensitivity was highly dependent on the insertion location, with near-loop insertions (ORR: 46%) being more sensitive than far-loop insertions (ORR: 0%). Putative mechanisms of acquired resistance to poziotinib included EGFR T790M, MET amplifications, and epithelial-to-mesenchymal transition (EMT). (Ref: Elamin YY et al. Cancer Cell. July 2022)
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In patients with recurrent mismatch repair proficient (MMRP) Endometrial Cancer, treatment with talazoparib and avelumab showed 11.4 % confirmed ORR and 22.9 % PFS at 6 months. Patients with homologous recombination repair (HRR) alterations and/or a platinum-free interval (PFI) of ≥6 months were more likely to derive clinical benefit compared with non–HRR-altered tumors and/or PFI ≤6 months and exhibited better PFS.                          (Ref: Konstantinopoulos PA et al. JAMA Oncol. July 28, 2022.)

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In patients with previously untreated locally advanced or metastatic TNBC, the addition of pembrolizumab to chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine–carboplatin) resulted in significantly longer overall survival than chemotherapy alone in the CPS-10 subgroup (PD-L1 expression scores of ≥ 10). No new safety signals emerged. (Ref: Cortes J et al. N Engl J Med. July 21, 2022)
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Brentuximab vedotin plus standard chemotherapy (B+AVD group) showed a 6-year OS of 93.9% compared to standard chemotherapy (ABVD group) 89.4% in patients with previously untreated, stage III/ IV HL. Fewer patients in the B+AVD group received subsequent therapy, including transplantation, and had fewer second cancers compared to the ABVD group. (Ref: Ansell SM et al. N Engl J Med. July 13, 2022)
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