Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era.

BACKGROUND: Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy. METHODS: Two hundred and eighty-one dMMR mCRC patients (n = 54 from three prospective Phase 3 CAIRO trials; n = 227 from the Netherlands Cancer Registry). Overall survival was analysed from diagnosis of mCRC (OS), from initiation of first-line (OS1) and second-line (OS2) systemic treatment. Cox regression analysis examined prognostic factors. As comparison for OS 2746 MMR proficient mCRC patients were identified. RESULTS: Of 281 dMMR patients, 62% received first-line and 26% second-line treatment. Median OS was 16.0 months (13.8-19.6) with antitumour therapy and 2.5 months (1.8-3.5) in untreated patients. OS1 was 12.8 months (10.7-15.2) and OS2 6.2 months (5.4-8.9) in treated dMMR patients. Treated dMMR patients had a 7.6-month shorter median OS than pMMR patients. CONCLUSION: Available data from immunotherapy trials lack a control arm with standard systemic treatment. Given the poor outcome compared to the immunotherapy results, our data strongly suggest a survival benefit of immunotherapy in dMMR mCRC patients.

Management of good risk germ-cell tumours.

Following the implementation of cisplatin-containing combined chemotherapy, patients with good-risk metastatic germ-cell cancer have an excellent prognosis. Since the 1980s, bleomycin, etoposide and cisplatin (BEP) have become the standard chemotherapy regimen for these patients. In view of both the high curative potential of BEP chemotherapy and the treatment-related side-effects, trials were carried out in patients with the greatest chance of cure to develop regimens with an improved toxicity profile while maintaining efficacy. Following the results of these trials, the standard chemotherapy in good-risk disease has been reduced from four cycles of BEP (4BEP) to three cycles of BEP (3BEP). Four cycles of etoposide and cisplatin (4EP) is an alternative treatment regimen, with similar efficacy. Studies that explored additional adjustments in the BEP regimen to further decrease toxicity have shown that the lower threshold of efficacy has been reached, and that the efficacy of the chemotherapy is compromised. Especially during the last decade, important long-term side-effects after the treatment of germ-cell cancers have been recognized. Chemotherapy in patients with germ-cell cancer increases the risk of developing cardiovascular disease and second malignant neoplasms. Whether 3BEP or 4EP is the optimal chemotherapy regimen for the future remains to be identified. Possibly differences in acute and late toxicities attributed to chemotherapy might eventually identify the best strategy.