Patients with non-small-cell lung cancer respond best to salvage chemotherapy when pre-treated with PD-1/PD-L1 inhibitors

 Patients with advanced non-small-cell lung cancer (NSCLC) who require salvage chemotherapy are 30% more likely to achieve a partial response if they have been pre-treated with a PD-1/PD-L1 checkpoint inhibitor compared to those who have not, according to a study presented at the European Lung Cancer Conference (ELCC) 2017 in Geneva, Switzerland .

The preliminary findings could potentially open the door to a new way of sequencing cancer therapy, as reported by the study authors.

“Our results are of utmost importance for NSCLC patients,” said lead investigator Sacha Rothschild, MD, PhD, from University Hospital Basel, Department of Medicine, Division of Oncology, Switzerland.

“Checkpoint inhibitors are currently the standard of care for NSCLC patients in the 2nd-line setting after chemotherapy and are used for a subset of patients with high PD-L1 expression as front-line therapy. So far, it is unclear how to treat patients not responding to immune checkpoint inhibitors or progressing after initial response to these agents. The activity of conventional chemotherapy in this setting has not been investigated so far. Therefore, these results are good news for patients that progress after immunotherapy and are still fit enough to receive further palliative therapy.”

The retrospective analysis included 82 patients with stage IV NSCLC, including adenocarcinoma (n=63), squamous cell carcinoma (n=18), and one case of large cell carcinoma.

A total of 67 patients had been previously treated with a PD-1/PD-L1 inhibitors (cases) including 56 patients who received nivolumab, seven who had received pembrolizumab, and four who had received atezolizumab.

The other 15 patients who had not been treated with PD-1/PD-L1 inhibitors served as controls.

All patients had been pre-treated with chemotherapy, with a mean of 2.37 prior regimens among cases and 1.93 in controls.

Salvage chemotherapy included docetaxel (62%), pemetrexed (20%), paclitaxel (6%), and others (12%).

Computed tomography (CT) scans performed within the first month and then every six weeks showed a significantly higher partial response rate in cases compared to controls (27% vs 7%, odds ratio [OR] 0.3, P<0 .0001="" p="">

Stable disease was seen in 51% of cases and 53% of controls, and progressive disease was seen in 22% of cases versus 40% of controls.

Multiple logistic regression showed that age, gender, number of prior chemotherapy regimens, tumour histology, smoking status, or different salvage chemotherapy regimens were not independently associated with the likelihood of achieving partial response.

“At this point we can only speculate on the reasons for better response in those pre-treated with checkpoint inhibitors,” said Rothschild. “Probably the activation of the immune system by checkpoint inhibition might render tumour cells more sensitive to chemotherapy. Or chemotherapy may help the tumour-specific T-cells to enter the tumour microenvironment and to exert their function.”

Rothschild said investigations are ongoing into the duration of response and toxicity, and he cautioned that this finding must be further explored in larger and prospective cohorts.

Commenting on the study, Marina Garassino, MD, Head of Thoracic Medical Oncology, National Cancer Institute of Milan (Fondazione IRCCS Istituto Nazionale dei Tumori) was enthusiastic about the potential implications.

“This is the first research suggesting that chemotherapy could potentially work better after immunotherapy,” she said. “All of us treating patients with immunotherapy have had a feeling about this because we’ve seen unexpected results with some patients, but this is the first study in which this phenomenon is formally described. Although the results are very preliminary, they suggest that immunotherapy can change the natural history of the disease and the micro-environment of the tumour, therefore rendering it more sensitive to chemotherapy. This could potentially point to new areas of research and new sequences of treatment.”

Cognitive-Behavioral Therapy May Help Reduce Memory Problems in Cancer Survivors Who Have Received Chemotherapy

A new analysis indicates that a type of psychotherapy delivered by videoconference may help prevent some of the long-term memory issues caused by chemotherapy. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings point to a noninvasive way to help cancer survivors manage some of the negative effects of their treatment.

It’s estimated that approximately half of cancer patients who receive chemotherapy develop long-lasting changes in memory function such as trouble remembering conversational content or steps in a task. While the memory problems tend to be mild, they diminish quality of life in areas of job performance and family and social life well beyond cancer treatment. The causes of this problem and reasons why it does not affect every survivor remain unknown, and there is currently limited research on treatments for it.

A team led by Robert Ferguson, PhD, who is currently at the University of Pittsburgh Cancer Institute but was at the Eastern Maine Medical Center and Lafayette Family Cancer Center in Bangor, Maine, while conducting this research, developed a cognitive-behavioral therapy called “Memory and Attention Adaptation Training” (MAAT), which helps cancer survivors to increase awareness of situations where memory problems can arise and to develop skills to either prevent memory failure or to compensate for memory dysfunction.

In a small randomized study, 47 Caucasian breast cancer survivors who were an average of four years post-chemotherapy were assigned to eight visits of MAAT (30 to 45 minutes each visit) or supportive talk therapy for an identical time span. The intent of the supportive therapy was to control for the simple effects of interacting with a supportive clinician, or “behavioral placebo.” Both treatments were delivered over a videoconference network between health centers to minimize survivor travel. All participants completed questionnaires assessing perceived memory difficulty and anxiety about memory problems, and they were also tested over the phone with neuropsychological tests of verbal memory and processing speed, or the ability to automatically and fluently perform relatively easy cognitive tasks. Participants were evaluated again after the eight MAAT and supportive therapy videoconference visits, as well as two months after the conclusion of therapy.

Compared with participants who received supportive therapy, MAAT participants reported significantly fewer memory problems as well as improved processing speed posttreament. MAAT participants also reported much less anxiety about cognitive problems compared with supportive therapy participants 2 months after MAAT concluded, but this was not a statistically significant finding.

“This is what we believe is the first randomized study with an active control condition that demonstrates improvement in cognitive symptoms in breast cancer survivors with long-term memory complaints,” said Dr. Ferguson. “MAAT participants reported reduced anxiety and high satisfaction with this cognitive-behavioral, non-drug approach. Because treatment was delivered over videoconference device, this study demonstrates MAAT can be delivered electronically and survivors can reduce or eliminate travel to a cancer center. This can improve access to survivorship care.” He noted that more research is needed using a larger number of individuals with varied ethnic and cultural backgrounds and multiple clinicians delivering treatment.