Kristin Barber, APRN, AOCNP, FNP-BC, unpacks the FDA approval of durvalumab in combination with cisplatin and gemcitabine for patients with biliary tract cancers.
On September 2, 2022, the FDA approved durvalumab (Imfinzi) in combination with gemcitabine and cisplatin for patients with locally advanced or metastatic biliary tract cancers. According to Kristin Barber, APRN, AOCNP, FNP-BC, this approval shows that chemoimmunotherapy combinations may be ushering in a new standard of care for this patient population.
The approval was supported by findings from the phase 3 TOPAZ-1 trial (NCT03875235; n = 685) which found that the median overall survival (OS) with chemoimmunotherapy was 12.8 months (95% CI, 11.1-14) compared with 11.5 months (95% CI, 10.1-12.5) with chemotherapy alone. The median profession-free survival (PFS) was 7.2 months (95% CI, 6.7-7.4) vs 5.7 months (95% CI, 5.6-6.7), respectively. Ultimately, the overall response rate with durvalumab was 27% (95% CI, 22% -32%) compared with 19% (95% CI, 15%-23%) with placebo, respectively.1
Barber is an outpatient clinical educator and advanced oncology nurse practitioner specializing in gastrointestinal oncology at the University of Utah’s Huntsman Cancer Hospital. Following the recent approval, Barber met with Oncology Nursing News® to offer a nursing perspective on this combination and how care is continuing to evolve for patients with biliary tract cancers.
Oncology Nursing News®:Could you comment on the findings from the phase 3 TOPAZ-1 trial? What about the data stood out to you?
TOPAZ-1 has offered a new standard of care first line regimen for biliary tract cancers. [The benefit of durvalumab] is a major finding since the previous standard of cisplatin/gemcitabine has been in place since the ABC-02 trial in 2010 (NCT00262769).
In TOPAZ-1, OS improved from 11.5 to 12.8 months in the chemoimmunotherapy study arm. Although this is only a modest improvement, the tail of the curve for gemcitabine/cisplatin/durvalumab seemed to plateau at 24 months whereas with the control arm of gemcitabine and cisplatin, it appeared to decline. This is similar to what we have seen with other immunotherapy trials.
Historically, what have been some of the challenges in treating biliary tract cancers? How might this approval represent a change in standard of care?
This approval definitely represents a change to the standard of care treatment for advanced and unresectable biliary tract cancer. At this time, combination immunotherapy and chemotherapy with durvalumab, gemcitabine, and cisplatin should be considered as first-line treatment for all patients.
Challenges in treating this population of patients include a lack of effective [treatment options], but this too has evolved dramatically in the past few years with the genomic sequencing of advanced biliary tract cancers. Every patient with biliary tract cancer now needs to have next-generation sequencing done because there is the potential to identify actionable targets such as FGFR fusions, IDH1 mutations, NTRK fusions, MSI [microsatellite instability]-high cancers and HER2 amplifications. All of these targets now have FDA approved drugs that can be used for treatment of biliary tract cancer in the second or later lines of therapy.
Does this approval reflect a greater shift towards immunotherapy treatments for gastrointestinal (GI) cancers? What are some of the advantages and limitations of immunotherapy in this space?
In GI cancers, the efficacy of immunotherapy overall has been limited, but this [has been] evolving quickly over the past few years. We have had great success with immunotherapy for MSI-high cancers. It has been first line therapy for our hepatocellular cancers (HCC) in combination with bevacizumab [Avastin] and then it also moved to first line therapy in combination with chemotherapy for [patients with] advanced and metastatic esophageal adenocarcinomas.
The most important advantages are for our patients that have more durable responses without significant toxicities. Alternatively, we have added chemotherapeutic agents to make triplet-based therapies for some GI cancers but this does often come with increased toxicities such as cytopenias, nausea, vomiting, and diarrhea.
What should nurses be aware of regarding the safety profile of durvalumab? Are there any necessary premedications?
In the TOPAZ-1 trial the addition of durvalumab to gemcitabine and cisplatin yielded similar adverse events (AEs) as chemotherapy plus placebo. For example, the total incidence of AEs was 99.4% in the experimental arm and 99.8% in the control group. The rate of grade 3 or 4 AEs were 75.7% in the study arm and 77.8% in the control arm, and treatment discontinuation rates because of AEs were higher in the control group vs the immunotherapy group at 15.2% and 13%, respectively. Lastly, the rate of immune-mediated AEs were 12.7% in the study arm and 4.7% in the control arm.
We educate our nurses who are caring for patients on this regimen to be aware of the chemotherapy associated AEs such as cytopenias, kidney function, hydration, electrolytes, nausea and vomiting. When we add the durvalumab we also need to screen for any immune-mediated AEs and then check regular thyroid function every 6 weeks. In my practice, we may also premedicate with Aloxi [palonosetron], dexamethasone, and Emend [aprepitant].
The drug comes with warnings for immune-mediated adverse events. What do best nursing practices look like in terms of monitoring and potentially responding to these AEs?
Since the immune-mediated AEs can take place in any organ we must educate patients to let us know about any new problems or concerns.
In clinic, patients are screened for any new onset diarrhea, cough, rash, or severe fatigue. They also get labs to check renal and hepatic function on day 1 and then [thyroid hormone levels] with reflux to T4 every 6 weeks. If any symptom is identified, the nurse discusses this with the advanced practice provider [APP] or the physician to see if any workup needs to be completed and if treatment needs to be held.
In our institution these patients see a MD or APP on day 1 of their cycle and then only see the infusion nurses with labs on day 8. This allows for the infusion nurse to assess and triage any concerns the patient may be having.
FDA approves durvalumab for locally advanced or metastatic biliary tract cancer. FDA. September 2, 2022. Accessed October 4, 2022. bit.ly/3LDKkyJ