PracticeUpdate: Oncology - Winter 2018

EXPERT OPINIONS 21

6 I will be very judicious in referring patients for HIPEC therapy. The French PRODIGE 7 trial of 265 patients, as reported by Quenet et al demonstrated that cytoreductive surgery in patients with intraperitoneal metastatic colorectal cancer was encouraging, with 41-month median overall survival, but the addi- tion of HIPEC (with oxaliplatin) did not improve overall disease-free or overall survival in the entire population. 7 However, there may be a subset of patients with intermedi- ate disease who may benefit. Two additional randomized studies are maturing; so, hopefully, we will have a more definitive answer in the future. Nonetheless, although there was no chemotherapy-only arm, selected patients appear to benefit from cytore- ductive surgery. 7 I will not recommend nephrectomy for all patients with metastatic renal cell cancer who are being treated with sunitinib (and, by extrapolation, with other targeted agents) . The results of the 450 patient CARMENA trial were reported by Mejean et al. 8 This trial demonstrated that sunitinib alone was noninferior to the addition of surgery in patients who present with stage IV disease. Accrual was slow over 8 years, and not all patients received the assigned treatment; but, none- theless, there was a statistically significant improvement in overall clinical benefit in patients who did not undergo nephrectomy. 8 I will be using more checkpoint inhibitors as first-line treatment for meta- static NSCLC. The landscape is rapidly changing, and ongoing studies are maturing in terms of final overall survival results. Ideally, in addition to PDL-1 testing, next-generation sequencing of the cancer should be performed in most patients as the results will lead to targeted therapy in patients with appropriate mutations. Determination of tumor mutational burden (TMB) is becoming increas- ingly used to select treatment as those patients with a high TMB seem to respond better to immune therapy. In addition to updated results from the IMpower131 study 9 and CheckMate 227 10 presented at the NSCLC session, Lopes et al presented at the plenary session the results of Keynote-042. 11 This international study of over 1200 patients with previously untreated advanced NSCLC and PDL-1 expression of at least 1% demonstrated a significant improvement in overall survival in patients treated with pembrolizumab versus combination chemotherapy. There was a higher response rate and duration of response in those treated with immunotherapy and significantly less toxicity. It was noted that crossover was not allowed per protocol, although a signif- icant number of patients did receive the alternate treatment. There were excellent discussions by Dr. Gandhi at the plenary session and Dr. Stinchcombe at the NSCLC session, both of whom stressed that there is no one preferred treatment of choice for advanced NSCLC. They provided guidelines for rational treatment choices based on tumor biology. 9 I will discuss with all premenopausal breast cancer patients the benefit of adding ovarian function suppression (OFS) to their adjuvant regimen and highly recommend it to higher-risk patients. Noh et al presented data from the Korean ASTRRA study, in which premenopausal women treated with adju- vant chemotherapy and tamoxifen were randomized to 2 years of OFS or just tamoxifen alone. There was a statistically significant improvement in both disease-free and overall survival in the 635 patients who received OFS as opposed to the 647 patients treated with tamoxifen alone. 12 The patient population was expanded by including patients who became premenopausal again (defined by menses and/or FSH <30) within 2 years of completing chemotherapy. In a related presentation, Regan et al updated results from the international SOFT and TEXT trials and concluded that premenopausal women at higher risk for recurrence benefitted most from OFS and also that the higher-risk patients had better disease-free survival with exemestane/OFS as opposed to tamox- ifen/OFS. 13 The very low-risk patients had excellent outcomes with tamoxifen alone. 10 I will be using adjuvant mFOLFIRINOX as adjuvant therapy for many patients with resected pancreatic cancer. As presented by Conroy et al in the French PRODIGE 24 randomized phase III trial of close to 500 patients, those randomized to mFOLFIRINOX as compared with single-agent gemcitabine had a significant improvement in disease-free (21.6 vs. 8 months) and overall survival (54.4 vs. 34.4 months), with an expected increase in grade 3/4 toxicities (75.5% vs. 51.1 %). 14 Median follow-up currently is 30.5 months. Despite the toxicity, these are very impressive results, and this regimen can be offered to appropri- ate patients. www.practiceupdate.com/c/69307

References 1. Sparano JA, Gray RJ, Wood WC, et al TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2- negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score. Paper presented at: ASCO 2018, Chicago, IL. Abstract LBA1. 2. Kunz PL, Catalano PJ, Nimeiri H, et al. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: A trial of the ECOG-ACRIN Cancer Research Group (E2211). Paper presented at: ASCO 2018, Chicago, IL. Abstract 4004. 3. Earl HM, Hiller L, Vallier A-L, et al. PERSEPHONE: 6 versus 12 months (m) of adjuvant trastuzumab in patients (pts) with HER2 positive (+) early breast cancer (EBC): Randomised phase 3 non-inferiority trial with definitive 4-year (yr) disease-free survival (DFS) results. Paper presented at: ASCO 2018, Chicago, IL. Abstract 506. 4. Hong YS, Kim SY, Lee JS, et al. Long-term results of the ADORE trial: Adjuvant oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) versus 5-fluorouracil and leucovorin (FL) after preoperative chemoradiotherapy and surgery for locally advanced rectal cancer. Paper presented at: ASCO 2018, Chicago, IL. Abstract 3501. 5. Gnant M, Pfeiler G, Steger GG, et al. Adjuvant denosumab in early breast cancer: Disease-free survival analysis of 3,425 postmenopausal patients in the ABCSG-18 trial. Paper presented at: ASCO 2018, Chicago, IL. Abstract 500. 6. Coleman RE, Finkelstein D, Barrios CH, et al. Adjuvant denosumab in early breast cancer: First results from the international multicenter randomized phase III placebo controlled D-CARE study. Paper presented at: ASCO 2018, Chicago, IL. Abstract 501. 7. Quenet F, Elias D, Roca L, et al. A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7. Paper presented at: ASCO 2018, Chicago, IL. Abstract LBA3503. 8. Mejean A, Escudier B, Thezenas S, et al. CARMENA: Cytoreductive nephrectomy followed by sunitinib versus sunitinib alone in metastatic renal cell carcinoma—Results of a phase III noninferiority trial. Paper presented at: ASCO 2018, Chicago, IL. Abstract LBA3. 9. Jotte RM, Cappuzzo F, Vynnychenko I, et al. IMpower131: Primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. Paper presented at: ASCO 2018, Chicago, IL. Abstract LBA9000. 10. Borghaei H, Hellmann MD, Paz-Ares LG, et al. Nivolumab (Nivo) + platinum-doublet chemotherapy (Chemo) vs chemo as first-line (1L) treatment (Tx) for advanced non-small cell lung cancer (NSCLC) with <1% tumor PD-L1 expression: Results from CheckMate 227. Paper presented at: ASCO 2018, Chicago, IL. Abstract 9001. 11. Lopes G, Wu Y-L, Kudaba I, et al. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: Open-label, phase 3 KEYNOTE-042 study. Paper presented at: ASCO 2018, Chicago, IL. Abstract LBA4. 12. Noh WC, Lee JW, Nam SJ, et al. Role of adding ovarian function suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or resume menstruation after chemotherapy: The ASTRRA study. Paper presented at: ASCO 2018, Chicago, IL. Abstract 502. 13. Regan MM, Francis PA, Pagani O, et al. Absolute improvements in freedom from distant recurrence with adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) HER2- negative breast cancer (BC): Results from TEXT and SOFT. Paper presented at: ASCO 2018, Chicago, IL. Abstract 503. 14. Conroy T, Hammel P, Hebbar M, et al Unicancer GI PRODIGE 24/CCTG PA.6 trial: A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas. Paper presented at:ASCO 2018, Chicago, IL. Abstract LBA4001.

VOL. 2 • NO. 3 • 2018