Clinicians tend to avoid placing patients on phase 1 trials unless necessary. However, new research shows that enrollment in phase 1 trials could be beneficial for patients with advanced ovarian cancer.
Enrollment in phase 1 clinical trials is often considered unhelpful for patients with heavily pretreated ovarian cancer since those patients sometimes have a poor prognosis. However, new data published in Cancer suggests that enrollment in early phase clinical trials are not only beneficial for patients but also represents a reasonable treatment option.
Although results from the Surveillance, Epidemiology and End Results (SEER) data analysis show mortality rates have gone down in patients with ovarian cancer in the past 10 years, patients with advanced-stage ovarian cancer have a 5-year survival rate less than 30%. Additionally, more than 80% of patients diagnosed with ovarian cancer will have their disease return, which can ultimately lead to platinum therapy resistance.
For these patients, many clinicians put them on clinical trials to access new treatments that may benefit them. However, late-stage clinical trials are the ones patients are often recommended due to the higher potential for a clinical benefit and a more predictable toxicity profile. But according to the data in Cancer, patients with heavily pretreated ovarian cancer had a median overall survival of 11.3 months when enrolled on phase 1 trials.
“Clinical trial design has significantly evolved over the past several decades, specifically with the objective of bringing modern therapeutic options to patients in a timely manner,” the authors wrote. “The backbone of trial design has been to sequence from phase 1 to phase 3 with the ultimate goals of improved patient outcomes, a favorable safety profile, and U.S. Food and Drug Administration Approval.”
It’s this backbone that often leads to excluding patients from phase 1 trials unless necessary. But researchers looked at data from 132 previously treated patients with ovarian cancer on phase 1 trials at the University of Colorado Cancer Center, from January 2008 to December 2018. This retrospective analysis not only identified a favorable overall survival rate but also an overall response rate, which is the rate of patients with both complete and partial responses to treatment, of 14.7%. Moreover, a median progression-free survival of 2.5 months was identified.
“In addition to an acceptable predicted level of toxicity, the potential for the clinical benefit of treatment with an investigational drug on a phase 1 trial is an important consideration,” they wrote.
None of the patients in the study died from treatment-related toxicities and only 19 patients discontinued treatment due to side effects. However, 75% discontinued treatment as a result of disease progression.
This is the first study, according to the authors, to evaluate this patient population treated on phase 1 trials. The authors did note, however, that phase 1 trials are not meant to assess efficacy outcomes and have other inherent limitations as they are the start of a treatment’s approval path. “Despite all of these limitations in the current single-institution study, response rates and (overall survival) for patients with ovarian cancer who are treated on phase 1 studies support this as a reasonable option for heavily pretreated patients,” the authors concluded.