Purpose

Despite the numerous benefits of physical activity (PA) for patients with cancer, many cancer survivors report challenges to participating in PA. The objectives of this study were (1) to assess barriers to PA and (2) to examine participant characteristics associated with modifiable barriers to PA among cancer survivors with pain.

Methods

We conducted a cross-sectional survey study at one academic medical center and 11 community hospitals. Participants completed the 12-item Physical Activity Barriers After Cancer (PABAC) instrument (Cronbach's alpha = 0.75). Multivariable regression models examined participant characteristics associated with PABAC scores with a higher score indicating more barriers to PA.

Results

Among 662 survivors, 67% had moderate or severe pain (rating 4 or greater on a scale of 0 to 10). Seventy-five percent of survivors did not meet the American Cancer Society PA recommendations on average, and these individuals had higher mean PABAC scores (beta coefficient (β) = 2.02, 95% confidence interval (CI) 0.96-3.09, p < 0.001). In adjusted analyses, cancer survivors who were non-white (β = 1.55, 0.28-2.82, p = 0.02), treated at a community hospital (β = 1.07, 0.09-2.05, p = 0.03), had surgery (β = 1.69, 0.69-2.69, p = 0.001), or within 12 months of diagnosis (β = 1.15, 0.20-2.10, p = 0.02) reported greater barriers to PA.

Conclusions

The majority of cancer survivors with pain are not adequately participating in PA. Key demographic and clinical characteristics are associated with survivors' barriers.

Implications for cancer survivors

Efforts to overcome specific barriers are needed to promote PA after a cancer diagnosis.

Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) account for ≤ 12% of all EGFR-mutant nonsmall cell lung cancers. We analysed real-world datasets to determine the frequency of ex20ins variants, and the ability of polymerase chain reaction (PCR) and next-generation sequencing (NGS) to identify them. Three real-world United States NGS databases were used: GENIE, FoundationInsights, and GuardantINFORM. Mutation profiles consistent with in-frame EGFR ex20ins were summarized. GENIE, FoundationInsights, and GuardantINFORM datasets identified 180, 627, and 627 patients with EGFR ex20ins respectively. The most frequent insertion region of exon 20 was the near loop (~ 70%), followed by the far loop (~ 30%) and the helical (~ 3-6%) regions. GENIE, FoundationInsights, and GuardantINFORM datasets identified 41, 102, and 96 unique variants respectively. An analysis of variants projected that ~ 50% of EGFR ex20ins identified by NGS would have been missed by PCR-based assays. Given the breadth of EGFR ex20ins identified in the real-world US datasets, the ability of PCR to identify these mutations is limited. NGS platforms are more appropriate to identify patients likely to benefit from EGFR ex20ins-targeted therapies.

Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) often develop resistance to current standard third-generation EGFR tyrosine kinase inhibitors (TKIs); no targeted treatments are approved in the osimertinib-relapsed setting. In this open-label, dose-escalation and dose-expansion phase 1 trial, the potential for improved anti-tumor activity by combining amivantamab, an EGFR-MET bispecific antibody, with lazertinib, a third-generation EGFR TKI, was evaluated in patients with EGFR-mutant NSCLC whose disease progressed on third-generation TKI monotherapy but were chemotherapy naive (CHRYSALIS cohort E). In the dose-escalation phase, the recommended phase 2 combination dose was established; in the dose-expansion phase, the primary endpoints were safety and overall response rate, and key secondary endpoints included progression-free survival and overall survival. The safety profile of amivantamab and lazertinib was generally consistent with previous experience of each agent alone, with 4% experiencing grade ≥3 events; no new safety signals were identified. In an exploratory cohort of 45 patients who were enrolled without biomarker selection, the primary endpoint of investigator-assessed overall response rate was 36% (95% confidence interval, 22-51). The median duration of response was 9.6 months, and the median progression-free survival was 4.9 months. Next-generation sequencing and immunohistochemistry analyses identified high EGFR and/or MET expression as potential predictive biomarkers of response, which will need to be validated with prospective assessment. ClinicalTrials.gov identifier: NCT02609776 .