While Slick battles it out with the non-believers, I thought I might drop a little information about the treatment of non-small cell lung cancer (NSCLC) and a brief on trial results with Keytruda, a PD1 inhibitor.
Currently, NSCLC is the most common of all lung cancers accounting for 84% of all cases. In 2018, there were 2 million new lung cancer cases accounting for 11.6% of the cancer incidence globally. Lung cancer is by far the leading cause of death worldwide, accounting for 25% of all cancer deaths. Currently, PD1 expression is a significant factor that influences the choice of treatment for NSCLC. The current approach is guided by The American Society of Clinical Oncology and Ontario Health, where patients with PD-L1 expression greater than 50% are typically offered monotherapy with the anti-PD-1 antibody pembrolizumab (Keytruda), although some with rapidly progressing or very extensive disease may be treated with a platinum doublet chemotherapy plus pembrolizumab. For patients with PD-L1 expression less than 50%, the combination of a platinum-doublet chemotherapy and pembrolizumab (Keytruda) is standard. However, there are current concerns with the use of PD1 inhibitors, like Keytruda, particularly in patients with epidermal growth factor receptor mutations as there is increased risk of pulmonary toxicity in these groups.
I believe that the KEYNOTE-021 trial is important, as it set the scene for PD1 inhibitors to be used in combination with chemotheraputic agents.
The
KEYNOTE-021 trial included 123 patients and was an important milestone for Keytruda, as the results of this study led to initial accelerated approval of combination therapy with carboplatin, pemetrexed, and pembrolizumab for patients with advanced, untreated, nonsquamous NSCLC without activating epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alterations. The addition of pembrolizumab provided a PFS of 13 versus 6 months and HR for disease progression or death 0.53 [95% CI 0.31-0.91].
And as a forward thought:
The results of the
KEYNOTE-189trial were quite impressive with the addition of pembrolizumab to chemotherapy improving 12-month overall survival (OS) rates relative to chemotherapy alone provided a HR for death of 0.49 [95% CI 0.38-0.64]. Twelve-month OS improvements were observed in all PD-L1 categories, with the greatest numerical differences observed in PD-L1-expressing tumors:
•<1 percent – 62 versus 52 percent (HR 0.59, 95% CI 0.38-0.92)
•1 to 49 percent – 72 versus 51 percent (HR 0.55, 95% CI 0.34-0.90)
•≥50 percent – 73 versus 48 percent (HR 0.42, 95% CI 0.26-0.68)
Long-term follow-up from the trial showed that estimated median OS in those receiving chemotherapy with or without pembrolizumab was 22 versus 11 months. Median progression-free survival (PFS) also improved with the addition of pembrolizumab with 8.8 versus 4.9 months and a HR for disease progression or death of 0.52 [95% CI 0.43-0.64]. The HR for PFS was less than 1.0 across all subgroups of PD-L1 expression, with the greatest effect seen in the >50% PD-L1 group (HR, 0.36 for PD-L1 ≥50 percent; HR, 0.55 for PD-L1 1 to 49 percent; and HR, 0.75 for PD-L1 <1 percent). What I found interesting was severe adverse events (≥grade 3) occurred in 67 percent of the patients in the pembrolizumab-combination group and in 66 percent of those in the placebo-combination group, with improved patient-reported quality of life.
If PD-1 is to set the scene for immunotherapy, then I think it has some big shoes to fill. I am confident that B-cell therapy in the future and it will be good to see if the IMU team can show efficacy like Keytruda.
The HR in the KEYNOTE-021 study of
0.53 [95% CI 0.31-0.91]looks awefully similar to the HR demonstrated in the HER-Vaxx interum results reported recently:
All IMO
(20min delay)
