The abscopal effect of immune-radiation therapy in recurrent and metastatic cervical cancer: a narrative review.

Despite human papillomavirus vaccination and screening, in about 5% of cases, cervical cancer (CC) is discovered at an initial metastatic stage. Moreover, nearly one-third of patients with locally advanced CC (LACC) will have a recurrence of their disease during follow-up. At the stage of recurrent or metastatic CC, there are very few treatment options. They are considered incurable with a very poor prognosis. For many years, the standard of care was the combination of platinum-based drug and paclitaxel with the possible addition of bevacizumab. The most recent years have seen the development of the use of immune checkpoint inhibitors (ICIs) (pembrolizumab, cemiplimab and others) in patients with CC. They have shown long term responses with improved overall survival of patients in 1st line (in addition to chemotherapy) or 2nd line (as monotherapy) treatment. Another emerging drug is tisotumab vedotin, an antibody-drug conjugate targeting tissue factor. Radiation therapy (RT) often has a limited palliative indication in metastatic cancers. However, it has been observed that RT can induce tumor shrinkage both in distant metastatic tumors beyond the radiation field and in primary irradiated tumors. This is a rarely observed phenomenon, called abscopal effect, which is thought to be related to the immune system and allows a tumor response throughout the body. It would be the activation of the immune system induced by the irradiation of cancer cells that would lead to a specific type of apoptosis, the immunogenic cell death. Today, there is a growing consensus that combining RT with ICIs may boost abscopal response or cure rates for various cancers. Here we will review the potential abscopal effect of immune-radiation therapy in metastatic cervical cancer.

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29).

Background: Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer. Methods: CAP29 is a retrospective, observational, multicenter real-life study conducted in 6 French centers. We evaluated efficacy of first-line setting chemotherapy plus pembrolizumab (November 2019 to September 2020) in advanced (stage III-IV) non-squamous non-small cell lung cancer patients without targetable alterations. Primary endpoint was progression-free survival. Secondary endpoints were overall survival, objective response rate and safety. Results: With a median follow-up of 4.5 months (0 to 22 months), a total of 121 patients were included. Baseline characteristics were: median age of 59.8 years with 7.4% ≥75 years, 58.7% of males, 91.8% PS 0-1, 87.6% of stage IV with ≥3 metastatic sites in 62% of cases. Patients had brain and liver metastases in 24% and 15.7% of cases, respectively. PD-L1 was <1% (44.6%), 1-49% (28.1%) and ≥50% (21.5%). Median progression-free survival and overall survival achieved 9 and 20.6 months, respectively. Objective response rate was 63.7% with 7 prolonged complete responses. Survival benefit seemed to be correlated with PD-L1 expression. Brain and liver metastases were not statistically associated with decreased overall survival. Most common adverse events were asthenia (76%), anemia (61.2%), nausea (53.7%), decreased appetite (37.2%) and liver cytolysis (34.7%). Renal and hepatic disorders were the main causes of pemetrexed discontinuation. Grade 3-4 adverse events concerned 17.5% of patients. Two treatment-related deaths were reported. Conclusions: First-line pembrolizumab plus chemotherapy confirmed real-life efficacy for patients with advanced non-squamous non-small cell lung cancer. With median progression-free survival and overall survival of 9.0 and 20.6 months, respectively and no new safety signal, our real-life data are very close to results provided by clinical trials, confirming the benefit and the manageable toxicity profile of this combination.

Real-life second-line epirubicin-paclitaxel regimen as treatment of relapsed small-cell lung cancer: EpiTax study.

BACKGROUND: Few therapeutic options are approved as second-line treatment after failure of platinum-based chemotherapy for patients with extensive-stage small-cell lung cancer (ES-SCLC). Topotecan widespread use remains challenged by the risk of severe toxicities in a pretreated population. Little is known about the efficacy and safety of epirubicin-paclitaxel doublet in second-line and beyond and especially cerebral outcomes. METHODS: EpiTax is a retrospective multicenter observational real-life study. We evaluated the efficacy of epirubicin 90 mg/m2 combined with paclitaxel 175 mg/m2 every 3 weeks in SCLC patients after failure of at least one line of platinum-based chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), intracranial control rate (ICR), and safety. RESULTS: A total of 29 patients were included. The median of previous systemic therapy lines was 2 (1-4). Eleven patients received the treatment in the second line. Characteristics of patients were a median age of 60 years (45-77), 65.5% of males with 72.4% of PS 0-1. Fifteen patients had a history of brain metastases. Median PFS and OS achieved 11.0 (95% CI, 8.1-16.3) and 23 (95% CI, 14.1-29.6) weeks, respectively. ORR was 34.5% and DCR was 55.2%. ICR was 3/15 (20%). Grade 3-4 adverse events were mainly hematological and concerned 7 patients. No case of febrile neutropenia or toxic death was reported. CONCLUSION: Epirubicin-paclitaxel association highlighted promising efficacy with PFS and OS of 11 and 23 weeks, respectively, ORR of 34.5%, and a tolerable safety profile. This doublet could represent another valuable therapeutic option for ES-SCLC patients treated in the second line and beyond.

Sweet syndrome induced by radiations during breast cancer treatment.

During the follow-up of a woman treated by radiotherapy for an in situ carcinoma of her left breast, radio-induced skin lesions were diagnosed. They appeared not to be simple radiodermatitis but radio-induced Sweet syndrome. Discussions were led on the benefit of completing the last session of radiotherapy for such a low-grade malignancy while considering the risk of complication from radio-induced disease. General and local corticotherapy rapidly eradicated the fever and asthenia, while the skin lesions disappeared gradually. Moreover, biological improvement was noticed. The presented features of Sweet syndrome are almost similar in their initial phase to the radiodermatitis that is seen in common medical conditions.

[Crushing or opening medication: what practices, what risks?] / Écrasement ou ouverture des médicaments : quelles pratiques, quels risques ?

The practice of crushing tablets or opening up capsules to be taken orally, when it is not prescribed, can affect the efficacy of a treatment, or even cause an adverse event. A survey carried out in 2016 revealed that this is a common practice, especially among elderly people. However, alternative forms exist and can be prescribed.