Most Read Articles
17 Jun 2019
Podcast: Dr Sara Hurvitz highlights that the addition of ribociclib to endocrine therapy improved overall survival in premenopausal women with HR+, HER2- advanced breast cancer, according to the MONALEESA-7 trial.
30 Nov 2018
New drug applications approved by US FDA as of 16 - 30 November 2018 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.
Roshini Claire Anthony, 2 days ago

A combination of tocilizumab and methotrexate reduced disease activity at 2 years compared with methotrexate plus prednisone in patients with early rheumatoid arthritis (RA), an effect not demonstrated with tocilizumab monotherapy.

Roshini Claire Anthony, 3 days ago

Patients referred to home hospice care following non-cancer diagnoses had their preventative medications significantly reduced between admission and death, though this did not apply to patients with cancer referred to hospice care, a retrospective study from Singapore showed.

Durvalumab shows OS benefit over chemo in NSCLC

Audrey Abella
03 May 2019

First-line therapy with the anti-programmed death ligand-1 (PD-L1) monoclonal antibody durvalumab improved overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC) compared with platinum-based chemotherapy (CT), according to results from two analyses of the MYSTIC* trial presented at ELCC 2019.

This phase 3 trial randomized immunotherapy/CT-naïve individuals 1:1:1 to receive durvalumab 20 mg/kg Q4W alone or with the anti-CTLA-4** antibody tremelimumab 1 mg/kg Q4W (four cycles), or platinum-based CT (up to six cycles).

 

OS in relevant subgroups

In a subgroup analysis evaluating 488 participants, durvalumab alone generated OS improvement compared with CT across most clinical subgroups, including those aged ≥65 years (hazard ratio [HR], 0.66), with non-squamous histology (HR, 0.70), with PD-L1 tumour cell (TC) ≥25 percent (HR, 0.63), and with ECOG performance status 0 (HR, 0.54). The durvalumab-tremelimumab combination provided a similarly improved OS vs CT across the same subgroups (HR, 0.72, 0.84, 0.64, and 0.76, respectively). [ELCC 2019, abstract LBA3]

The favourable HRs for durvalumab were consistent with the overall primary analysis results, which reflected a clinically meaningful OS improvement with durvalumab vs CT in individuals with PD-L1 TC ≥25 percent (median, 16.3 vs 12.9 months, HR, 0.76, 97.54 percent confidence interval [CI], 0.56–1.02; p=0.036). Albeit nonsignificant, the durvalumab-tremelimumab combination also generated a numerical improvement compared with CT (HR, 0.85, 98.77 percent CI, 0.61–1.17; p=0.202). 

However, the durvalumab-tremelimumab combo was associated with the highest incidence of treatment-related*** adverse events (TRAEs) leading to discontinuation (13.2 percent), followed by CT and durvalumab monotherapy (9.4 percent and 5.4 percent, respectively). Immune-mediated# AEs were also highest with durvalumab-tremelimumab (28.3 percent) compared with durvalumab monotherapy and CT (13.6 percent and 3.4 percent, respectively).

Nonetheless, the safety profile of durvalumab was deemed manageable and consistent with previous studies, noted the researchers, highlighting the higher incidence of grade ≥3 TRAEs in the CT vs the durvalumab arms (33.8 percent vs 14.9 percent [durvalumab monotherapy] and 22.9 percent [durvalumab + tremelimumab]).

 

Subsequent immunotherapy

A majority of durvalumab and CT recipients received subsequent therapy (44.8 percent and 58.6 percent, respectively), most of whom starting within 2 months of discontinuing treatment. Of these, 13.7 and 67.4 percent of those respective groups received immunotherapy, the most common being nivolumab and pembrolizumab. [ELCC 2019, abstract LBA4]

After adjusting for the effect of subsequent immunotherapy using a two-stage model, the OS benefit observed with durvalumab vs CT improved compared with the overall primary analysis results (median, 16.2 vs 11.5 months, HR, 0.66, 97.54 CI, 0.49–0.90; p=0.002).

However, the significantly higher proportion of CT-treated patients who received subsequent immunotherapy might have confounded the primary OS outcome, potentially masking the true efficacy of durvalumab, pointed out the researchers, hence the need for further evaluation.

 

 

Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Pharmacist - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
17 Jun 2019
Podcast: Dr Sara Hurvitz highlights that the addition of ribociclib to endocrine therapy improved overall survival in premenopausal women with HR+, HER2- advanced breast cancer, according to the MONALEESA-7 trial.
30 Nov 2018
New drug applications approved by US FDA as of 16 - 30 November 2018 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.
Roshini Claire Anthony, 2 days ago

A combination of tocilizumab and methotrexate reduced disease activity at 2 years compared with methotrexate plus prednisone in patients with early rheumatoid arthritis (RA), an effect not demonstrated with tocilizumab monotherapy.

Roshini Claire Anthony, 3 days ago

Patients referred to home hospice care following non-cancer diagnoses had their preventative medications significantly reduced between admission and death, though this did not apply to patients with cancer referred to hospice care, a retrospective study from Singapore showed.