Treatment of non-small-cell lung cancer after progression on nivolumab or pembrolizumab.

Background: Although PD-1 antibodies (PD1 Ab) are the standard of care for advanced non-small-cell lung cancer (ansclc), most patients will progress. We compared survival outcomes for patients with ansclc who received systemic therapy (st) after progression and for those who did not. Additionally, clinical characteristics that predicted receipt of st after PD1 Ab failure were evaluated. Methods: All patients with ansclc in British Columbia initiated on nivolumab or pembrolizumab between June 2015 and November 2017, with subsequent progression, were identified. Eligibility criteria for additional st included an Eastern Cooperative Oncology Group (ecog) performance status (ps) of 3 or less and survival for more than 30 days from the last PD1 Ab treatment. Post-progression survival (pps) was assessed by landmark analysis. Baseline characteristics associated with pps were identified by multivariable analysis. Results: Of 94 patients meeting the eligibility criteria, 33 received st after progression. In 75.6%, a PD1 Ab was received as first- or second-line treatment. The most common sts were erlotinib (36.4%) and docetaxel (27.3%). No statistically significant difference in median pps was observed between patients who did and did not receive st within 30 days of their last PD1 Ab treatment (6.9 months vs. 3.6 months, log-rank p = 0.15.) In multivariable analysis, factors associated with increased pps included an ecog ps of 0 or 1 compared with 2 or 3 [hazard ratio (hr): 0.42; 95% confidence interval (ci): 0.24 to 0.73; p = 0.002] and any response compared with no response to PD1 Ab (hr: 0.54; 95% ci: 0.33 to 0.90; p = 0.02). Conclusions: In this cohort, only 35.1% of patients eligible for post-PD1 Ab therapy received st. Post-progression survival was not significantly affected by receipt of post-progression therapy. Prospective trials are needed to clarify the benefit of post-PD1 Ab treatments.

Canadian perspectives: update on inhibition of ALK-positive tumours in advanced non-small-cell lung cancer.

Background: Inhibition of the anaplastic lymphoma kinase (alk) oncogenic driver in advanced non-small-cell lung carcinoma (nsclc) improves survival. In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK-positive patients, recommending use of the alk inhibitor crizotinib in the first line. New scientific literature warrants a consensus update. Methods: Clinical trials of alk inhibitor were reviewed to assess benefits, risks, and implications relative to current Canadian guidance in patients with ALK-positive nsclc. Results: Randomized phase iii trials have demonstrated clinical benefit for single-agent alectinib and ceritinib used in treatment-naïve patients and as second-line therapy after crizotinib. Phase ii trials have demonstrated activity for single-agent brigatinib and lorlatinib in further lines of therapy. Improved responses in brain metastases were observed for all second- and next/third-generation alk tyrosine kinase inhibitors in patients progressing on crizotinib. Canadian recommendations are therefore revised as follows:■ Patients with advanced nonsquamous nsclc have to be tested for the presence of an ALK rearrangement.■ Treatment-naïve patients with ALK-positive disease should initially be offered single-agent alectinib or ceritinib, or both sequentially.■ Crizotinib-refractory patients should be treated with single-agent alectinib or ceritinib, or both sequentially.■ Further treatments could include single-agent brigatinib or lorlatinib, or both sequentially.■ Patients progressing on alk tyrosine kinase inhibitors should be considered for pemetrexed-based chemotherapy.■ Other systemic therapies should be exhausted before immunotherapy is considered. Summary: Multiple lines of alk inhibition are now recommended for patients with advanced nsclc with an ALK rearrangement.

Breast cancer screening for women younger than 40.

The charts of 661 women aged 15 to 39 revealed that almost 50% of teenage patients had had breast screening examinations. Most of the physicians and residents involved began performing and teaching breast examination to patients in their teens. Concerned that it might do more harm than good, the Canadian guidelines do not advocate early screening.

PIP: In Canada, physicians reviewed the charts of 661 15-39 year old women who had attended the Toronto General Family Practice Unit in 1989 and, in February 1990, distributed a questionnaire to 38 physicians at the same clinic to examine the use of breast cancer screening by family physicians and at what age they begin screening. 2 women underwent a screening mammogram. 74.4% had undergone a breast examination during their visits. Physicians diagnosed an abnormality in 6 of these women, all older than 25 years old. The physicians ordered a diagnostic mammogram in all but 1 of these women. 3 women had a surgical consultation, 1 of whom had a breast biopsy. She was between 25 and 29 years old. The diagnosis is all 3 cases was benign breast problems. 6.5% of all women had a family history of breast cancer. They were not more likely to undergo a breast examination than were those with no such history, though. 41.6% of the women used oral contraceptives (OCs). They were more likely to undergo a breast examination than those who did not use OCs (p = .03). Just 1 of the physicians reported breast cancer in a sister or mother as the single most important risk factor for developing breast cancer besides age. All the physicians used screening mammography on women they considered to be at high risk of breast cancer and just 6 did for low risk women (p .000001). 84.2% were not familiar with the Canadian Task Force guidelines for clinical breast examination (i.e., it should be done annually on all women at least 40 years old). Most physicians taught women under 40 years old, and even teenagers, how to do a breast self-examination. Just 1 physician knew that the Task Force did not promote breast self-examination. It does not promote early screening, because it may do more harm than good. These findings indicated a need for a campaign to increase awareness about these guidelines and of the problems associated with screening younger women.