LUNG CANCER
Long-term outcomes and molecular correlates of sotorasib efficacy in patients with pretreated KRASG12C-mutated non-small-cell lung cancer: 2-year analysis of CodeBreaK 100
Recent research showed that about one-third of non-small cell lung cancer (NSCLC) patients who underwent treatment with sotorasib-a targeted therapy-survived for at least 2 years, according to long-term findings from the CodeBreak 100 clinical trial (J Clin Oncol 2023; doi:10.1200/JCO.22.02524). This multicenter, single-group, open-label Phase I/II study enrolled adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who had progressed on prior therapies. As of February 22, 2022, 174 were administered sotorasib 960 mg once daily. The median duration of treatment was 5.6 months and 13 patients remained on treatment at cutoff. Study authors observed an overall survival rate of 50.8 percent after 1 year and 32.5 percent after 2 years. The median overall survival was 12.5 months. Data showed that 40.7 percent of patients had a partial or complete response, with a median duration of response of 12.3 months. The median progression-free survival (PFS) was 6.3 months. Forty patients (23%) had long-term clinical benefit with a PFS of at least 12 months. This long-term analysis of sotorasib demonstrated a favorable safety profile and durable efficacy across subgroups.
"The findings from this analysis with over 2-year follow-up data demonstrate that nearly a quarter of previously treated advanced stage KRAS G12C-mutated NSCLC patients treated with sotorasib derived long-term benefit with few late-onset treatment-related toxicities, supporting not only its use in this treatment setting, but also additional studies investigating its therapeutic role in earlier lines of therapy," the study authors concluded.
AUTHOR COMMENTARY: "The 2-year survival is a landmark observation," noted first author Grace Dy, MD, Director of Thoracic Medicine Translational Research at Roswell Park Comprehensive Cancer Center. "We also found that there were long-term benefits in nearly a quarter of patients, meaning these patients had progression-free survival greater than 12 months. That is much higher than we anticipate with traditional chemotherapy."
PROSTATE CANCER
Addition of metastasis-directed therapy to intermittent hormone therapy for oligometastatic prostate cancer
Adding metastasis-directed radiation therapy (MDT) to intermittent hormone therapy improved progression-free survival (PFS) among patients with oligometastatic prostate cancer, according to Phase II findings that were recently published in JAMA Oncology (2023; doi: 10.1001/jamaoncol.2023.0161). The External Beam Radiation to Eliminate Nominal Metastatic Disease (EXTEND) trial is a Phase II basket randomized clinical trial examining the addition of MDT to standard-of-care systemic therapy in multiple solid tumors. The prostate intermittent hormone therapy basket included adult patients with oligometastatic prostate cancer who had five or fewer metastases and underwent hormone therapy for at least 2 months. Study participants were randomized 1:1 to MDT plus intermittent hormone therapy or hormone therapy alone. The primary endpoint was disease progression. A key secondary endpoint was eugonadal PFS, which was defined as the time from achieving a eugonadal testosterone level (>=150 ng/dL) until progression.
Eighty-seven men with a median age of 67 years were included in this analysis. At a median follow-up of 22 months, the median progression-free survival had not yet been reached among men in the combination therapy cohort. Comparatively, the median PFS was 15.8 months for patients who only received hormone therapy. The study authors also observed an improvement in eugonadal PFS among patients who received MDT. The median eugonadal PFS was not yet reached in this group versus 6.1 months in the hormone therapy-only cohort. Data showed that the treatment was well-tolerated with three Grade 3 toxicities reported in each arm. This included impaired muscle motion, as well as urinary and gastrointestinal side effects, all of which were easily managed.
"Combination of MDT with intermittent hormone therapy may allow for excellent disease control while facilitating prolonged eugonadal testosterone intervals," according to the study authors, who also noted that incorporating metastasis-directed therapy and intermittent hormones may be an option for individuals in this patient population who want to prolong hormone therapy cessation.
AUTHOR COMMENTARY: "This study shows that the combination of metastasis-directed radiation and intermittent hormone therapy significantly improved progression free-survival with manageable toxicities for patients with oligometastatic disease," said principal investigator Chad Tang, MD, Associate Professor of Radiation Oncology at the University of Texas MD Anderson Cancer Center. "I am encouraged that this data, combined with knowledge gained in future trials, will allow us to safely preserve a man's quality of life following this diagnosis."
BREAST CANCER
Interrupting endocrine therapy to attempt pregnancy after breast cancer
Temporarily pausing endocrine therapy to pursue a pregnancy did not raise the short-term risk of disease recurrence among certain women with hormone receptor-positive early breast cancer. This research also showed that almost 75 percent of study participants had at least one pregnancy and nearly 65 percent delivered healthy babies during their break from hormone therapy (N Engl J Med 2023; doi: 10.1056/NEJMoa2212856). The POSITIVE study (Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine-ResponsIVE Breast Cancer) recruited patients in 116 centers across 20 countries. The study enrolled 516 women who were 42 years old or younger and had Stage I, II, or III disease. They had undergone adjuvant endocrine therapy for 18-30 months and wanted to get pregnant. The primary endpoint was the number of breast cancer events-defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer-during follow-up. The breast cancer outcomes were compared with an external control cohort that included women who would have met the entry criteria for the POSITIVE trial.
At a median follow-up of 41 months, the study authors reported that 44 participants had experienced a recurrence of breast cancer. They observed a 3-year rate of recurrence of 8.9 percent, which was similar to the 9.2 percent rate seen in the external control group who did not pause endocrine therapy. The analysis followed 497 women for pregnancy status and found that 368 (74%) had at least one pregnancy and 317 (63.8%) had at least one live birth. A total of 365 babies were born. Resuming endocrine therapy after a pregnancy attempt or success was recommended. The research team continues to follow study participants to assess longer-term safety.
AUTHOR COMMENTARY: "Fortunately, the vast majority of young women with early-stage breast cancer are going to be cured of their disease," noted lead author Ann Partridge, MD, MPH, founder and Director of the Program for Young Adults with Breast Cancer at Dana-Farber Cancer Institute. "However, current treatment guidelines can often deprive women of the chance to start or grow their families. These data from the POSITIVE study show that many of our younger patients can safely pause their endocrine therapy to pursue pregnancy."