The phase 3 CALGB 9343 study significantly changed prescription patterns for patients with metastatic colorectal cancer, according to a presentation at the International Society for Pharmacoeconomics and Outcomes Research 2022.
While results from the AVEX trial (NCT00484939) examining bevacizumab in patients with metastatic colorectal cancer (CRC) did not demonstrate any large impact, the phase 3 CALGB 9343 study significantly changed prescription patterns for this patient population, according to findings revealed at the International Society for Pharmacoeconomics and Outcomes Research 2022.1
These conclusions suggest that gaining additional clinical evidence for older adults can result in having a significant impact on the clinical practice among these patients.
Findings were presented by Woojung Lee, PharmaD, in hopes to understand the increasing calls for clinical evidence for older adults. Further, investigators aimed to gain more knowledge of the impacts older adult-specific clinical trials have on clinical practice and the ways in which they can facilitate discussion around prioritizing and implementing such trials.
In this presentation, Lee noted that the effect of older adult-specific clinical trials on the prescription level was estimated using the phase 3 trial AVEX trial of bevacizumab in patients with CRC as well as irradiation in breast cancer in the CALGB 9343 trial.
For the AVEX study, patients with metastatic CRC were identified between 2010-2020 who received fluoropyrimidine in addition to bevacizumab as a first-line therapy using TriNetX data. Though this analysis looked at data from a 10-year time frame of patients enrolled in the AVEX study, from July 9, 2007, to Dec 14, 2010, a total of 280 patients with a median age of 76 years (range, 70–87) were enrolled from 40 sites across 10 countries. Patients were randomized and received either bevacizumab plus capecitabine (n = 140) or capecitabine alone (n = 140).2
Findings of this trial revealed that progression-free survival was significantly longer in patients who received bevacizumab in addition to capecitabine compared with capecitabine alone. The median PFS was 9.1 months)95% CI, 7.3-11.4 with the addition of bevacizumab vs 5.1 months (95% CI, 4.2-6.3) without (HR 0.53; 0.41-0.69]; P <0·0001).
In regard to safety, treatment-related adverse events (TRAE) deemed grade 3 or worse were observed in 53 (40%) patients enrolled in the combination group vs 30 (22%) in the capecitabine group. The most common grade 3 or higher adverse event (AE) of special interest for bevacizumab or chemotherapy were hand-foot syndrome (16% vs 7%), diarrhea (7% vs 7%), and venous thromboembolic events (8% vs 4%).
Treatment-related serious adverse events also were seen in 19 (14%) and 11 (8%) patients. Additionally, treatment-related deaths occurred in 5 patients who received bevacizumab in addition to capecitabine and 4 given capecitabine alone. The most common any-grade AE of special interest for bevacizumab was hemorrhage (34 [25%] vs nine [7%]).
This study showed that the combination of bevacizumab plus capecitabine was effective and a well-tolerated regimen for elderly patients with metastatic CRC.
As for the CALGB 9343 study, patients with stage I estrogen receptor (ER)-positive breast cancer treated by lumpectomy were identified using SEER registry data in 2000-2018.3
A total of 636 women aged 70 years and older with clinical stage I ER–positive breast cancer were randomly assigned to receive tamoxifen plus radiation therapy (n = 317) or tamoxifen alone (n = 319) Primary end points of the trial were time to local or regional recurrence, frequency of mastectomy, breast cancer–specific survival, time to distant metastasis, and overall survival (OS).
With the median follow-up for treated patients at 12.6 years, findings showed that when patients were examined at the 10-year mark, 98% of patients receiving tamoxifen plus radiation therapy (95% CI, 96%-99%) compared with 90% of those receiving tamoxifen alone (95% CI, 85%-93%) were free from local and regional recurrences. No significant differences were observed in regard to time to mastectomy, time to distant metastasis, breast cancer-specific survival, or OS between the 2 examined groups. At 10 years, the OS rate was 67% (95% CI, 62%-72%) and 66% (95% CI, 61%-71%) in the tamoxifen plus radiation therapy and tamoxifen alone groups, respectively.
These results showed that with this long-term follow-up, a previously observed small improvement in locoregional recurrence with the addition of radiation therapy remains, but this result did not translate into an advantage in OS, distant disease-free survival, or breast preservation. Tamoxifen remains an option for women aged 70 years and older with ER-positive early-stage breast cancer.
Within the study, experts performed a difference-in-differences analysis in order to examine the impact of AVEX and CALGB 9343 on the probability of bevacizumab and irradiation use, respectively, among patients older than 70-year-old compared to those younger than 70 years old.
In the 2 trials, a total of 2,416 patients with CRC and 243,587 with breast cancer were included. Findings showed that the AVEX study did not change the probability (β) of bevacizumab use at the time the study was published in 2013 (β =0.042; 95% CI, -0.065-0.150) and its trend overtime also was not changed after the publication in older patients (β =0.008; 95% CI, -0.042-0.057). While CALGB 9343 did not change the level of irradiation use at the time of its publication in 2004 (β=-0.013; 95% CI, -0.030-0.005), there was a significant decrease in the probability of irradiation use in older adults by 1 percentage point per year between 2004-2018 (95% CI, -0.016 to -0.004).
In 2010, follow-up results showed that there was a significantly accelerated average yearly effect by 1.7 percentage points (95% CI, -0.030 to -0.004). Further, in in 2013 results showed that there was no significant change in the average yearly effect (-0.009, 95% CI, -0.037-0.017) as well as in 2015 (β =0.032, 95% CI, -0.014-0.035).