Blogs

19 Sep Lurbinectedin in patients with pretreated germline BRCA1/2 metastatic breast cancer

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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12 Sep Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of IDO1

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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27 Aug Ripretinib Exhibits Better Tolerability Profile than Sunitinib in Advanced GIST Tumors

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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20 Aug Poziotinib Shows Clinical Benefit in EGFR Exon 20–Mutant NSCLC, Efficacy Dependent on Insertion Location.

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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13 Aug Talazoparib and Avelumab for Mismatch Repair Proficient Endometrial Cancer

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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08 Aug Pembrolizumab plus chemotherapy extends survival in triple-negative breast cancer

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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18 Jul Brentuximab Vedotin Improves Overall Survival in Treatment Naïve, Advanced Stage Hodgkin’s Lymphoma

18 Jun Capivasertib (AKT inhibitor) plus Fulvestrant Improves Survival in Aromatase Inhibitor Resistant, ER+/HER2- Advanced Breast Cancer

The addition of capivasertib to fulvestrant showed a significant PFS benefit in the original pathway-altered and non-altered subgroups. In the pathway altered subgroup, the median OS with the combination was significantly longer than fulvestrant alone. The expanded biomarker testing suggested that capivasertib predominantly benefits patients with PI3K/AKT/PTEN pathway-altered tumours. (Ref: Howell SJ et al.  Lancet Oncol. June 1, 2022)
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12 Jun Adagrasib (KRAS inhibitor) in Non–Small-Cell Lung Cancer Harboring a KRASG12C Mutation

In patients with KRASG12C-mutated NSCLC previously treated with platinum-based chemotherapy and checkpoint inhibitor therapy, adagrasib showed an objective response of 42.9%. Tumor shrinkage of any magnitude was observed in 79.5% patients (A). Intracranial tumor shrinkage was also seen (B). The median duration of response was 8.5 months (95% CI 6.2 to 13.8), the median PFS was 6.5 months (95% CI, 4.7 to 8.4) and the median overall survival was 12.6 months (95% CI, 9.2 to 19.2). The results were similar to sotorasib.
(Ref: Jänne PA et al. N Engl J Med. June 3, 2022)
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31 May Tiragolumab (TIGIT inhibitor) plus Atezolizumab shows promising Efficacy in PD-L1-positive advanced NSCLC

In chemotherapy-naïve, PD-L1-positive (tumour proportion score ≥1%) patients with locally advanced or metastatic NSCLC, tiragolumab plus atezolizumab showed a significant improvement in both objective response rate (ORR) and progression-free survival (PFS), with a stratified hazard ratio 0·57 [95% CI 0·37–0·90], p=0·015.
The combination was well tolerated, with a safety profile similar to that of atezolizumab alone. (Cho BC et al. The lancet Oncology May 13, 2022)
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