Immunotherapies swing for home runs in clinical trials
Immunotherapies swing for home runs in clinical trials
  • Park Sun-jae
  • 승인 2020.01.06 11:23
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Pembrolizumab extends indications to bladder cancer
Osimertinib nearly attains the status of first-line treatment for lung cancer
Abemaciclib+ Ribociclib+ Fulvestrant combo therapy rises as a game-changer in breast cancer

Baseball players and clinical trials have a lot in common. A baseball player swings numerous times to hit the ball but misses many times before hitting it out the field or scoring a home run. Clinical trials are no different. For an investigational compound to become a drug, it has to go through various clinical trial stages and face many failures along the way.

The anticancer drugs at-bat last year fared well. There were no home runs, but there were enough hits to maintain a notable batting average. Developments opened up a new chapter in the field of cancers with relatively poor prognoses such as pancreatic and lung cancer. Developers mainly gained praise for making strides in the area of pancreatic cancer, which was considered impenetrable.


Lung cancer drug pembrolizumab takes MVP

Pembrolizumab, a non-small cell lung cancer drug that was close to hitting a home run, continued its batting streak last year. It stole the spotlight for expanding its indications to bladder cancer when results from the phase 2 KEYNOTE-057 trial were announced in September at the European Society for Medical Oncology (ESMO) 2019 in Barcelona, Spain.

The complete response rate with pembrolizumab in 102 patients for 3 and 12 months, respectively, was 41.2% and 23.5%.

Based on the positive KEYNOTE-057 trial, MSD announced it recently applied for an additional bladder cancer indication to the US Food and Drug Administration (FDA). FDA’s Oncologic Drugs Advisory Committee (ODAC) is expected to review the application soon. 

MSD also presented five-year KEYNOTE-001 data on pembrolizumab last year at the American Society of Clinical Oncology’s (ASCO) annual conference that was held in Chicago from June 31 to July 4.

The five-year survival rate of patients who had no previous treatment was 23.2 percent, which was a reduction from the three-year survival rate of 37 percent. When analyzed by PD-L1 expression, 29.6 percent with PD-L1 expression of 50 percent or more were alive after five years, compared with 15.7 percent with PD-L1 expression levels below 50 percent.

Maybe expectations were too high. There were remarks that the five-year pembrolizumab data fell short, considering 23.2 percent of people who had not previously been treated with chemotherapy and 15.5 percent of previously treated patients were alive after five years.

Lung cancer drug osimertinib gets to first base

Osimertinib, an EGFR-positive non-small cell lung cancer drug, had to settle for getting to first base without striking out.

The FLAURA study’s data on overall survival presented at ESMO in September showed its possibility as first-line therapy but gave rise to some concerns.

Results showed that the median OS was 38.6 months in the osimertinib arm and 31.8 months in the control arm, indicating that osimertinib slashes the risk of death by 20 percent.

The median progression-free survival (PFS) was 18.9 months in the osimertinib arm and 10.2 months in the control arm. The three-year OS rate was 53.7 percent for osimertinib and 44.1 percent for the control. At the three years of treatment, 28 percent had continued osimertinib treatment, while only 9 percent continued with the therapy of the control arm.

Even though osimertinib succeeded in getting to first base, it failed to get further because the T790M mutation stood in the way.

“After disease progression, 31 percent of patients in the control group crossed over to the osimertinib arm, representing 47 percent of patients in the control group that received post-study therapy,” said study author Professor Suresh Ramalingam of Winship Cancer Institute of Emory University. “That is consistent with what we would expect in the real-world setting since only about 50% of patients develop the T790M mutation and will be candidates for osimertinib.”

Olaparib scores a hit in the impenetrable field of pancreatic cancer

AstaZeneca’s olaparib (product name Lynparza) did what mayn considered impossible and finally opened up the path to treating pancreatic cancer with results from its phase 3 POLO trial.

Olaparib  is an ovarian cancer-targeted drug that belongs to the family of oral poly ADP ribose polymerase (PARP) inhibitors.

Olaparib defied expectations by swinging the bat and hitting the ball, proving its efficacy in the POLO trial. The subjects were patients with gBRCAm-metastatic pancreatic cancer who had undergone platinum-based chemotherapy for more than 16 weeks as primary maintenance therapy at 119 medical institutions in 12 countries.

The median PFS, assessed as the primary endpoint, was 7.4 months for the olaparib group and 3.8 months for the control group. The risk of disease progression or death was also 47 percent lower in the olaparib group than in the placebo group(HR 0.53; 95% CI 0.35-0.82; P=0.004).

Some noted that olaparib could have done more since the drug did not improve the overall survival rate compared to the placebo group. However, experts point out that olaparib is a rising star that promises better outcomes in the year ahead.

Game changers abemaciclib+ribociclib+fulvestrant transform breast cancer landscape

A star has emerged in the field of breast cancer that could change the game altogether. This star appeared in clinical trials that had results good enough to be designated as game-changers.

The MONARCH 2 and MONALEESA-3 trial results, presented at ESMO, showed that the combination of Eli Lilly and Company’s abemaciclib (product name Verzenio), Novartis’ ribociclib (product name Kisqali), and fulvestrant (product name Faslodex) increased patient’s entire OS.

In the MONARCH 2 study, the survival of the combination group was approximately four years longer. The median OS was 46.7 months in the combination therapy group and 37,3 months in the fulvestrant alone group (HR 0.757; 95% CI 0.606-0.945; P=0.0137).

Median PFS was also 16.9 months in the combination group and 9.3 months in the control group. At three years, PFS was nearly three times higher in the combo group (29.9 vs. 10.1 percent).

The MONALEESA-3 study also showed that the OS in the control group was 40 months, while the OS was not reached in the combo group after an average of 39.4 months of follow-up(HR 0.724; 95% CI 0.568~0.924; P=0.00455).

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